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A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis.

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Terminated
CT.gov ID
NCT00471237
Collaborator
(none)
564
Enrollment
49
Locations
4
Arms
19.4
Actual Duration (Months)
11.5
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
564 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
May 14, 2007
Actual Primary Completion Date :
Dec 26, 2008
Actual Study Completion Date :
Dec 26, 2008

Arms and Interventions

Arm Intervention/Treatment
No Intervention: Placebo

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
Active Comparator: 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

Drug: Alendronate
Bisphosphonate
Active Comparator: 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

Drug: Teriparatide
PTH (1-34)
Experimental: 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.

Drug: Ronacaleret
100mg, 200mg, 300mg, 400mg
Other Names:
  • SB-751689

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    Secondary Outcome Measures

    1. 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.

    2. 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.

    3. 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%.

    4. 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.

    5. 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%.

    6. 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%.

    7. 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%.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    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]

      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.

    13. 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.

    14. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 79 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion:

    • Informed consent: Subject is willing and able to provide written informed consent.

    • Menopausal status: Ambulatory female aged < 80 years at screening and >5 years postmenopausal.

    • T-Score: A subject with either no or only one prevalent vertebral fracture is eligible for inclusion if she satisfies one of the following T-score requirements:

    If no prevalent vertebral fracture subject must have an absolute BMD value consistent with a T-score of less than or equal to -2.5 and greater than -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine, or If one prevalent vertebral fracture subject must have an absolute BMD value consistent with a T-score of less than or equal to -2.0 and greater than -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine.

    • Suitable vertebra: Two or more vertebra in the range of L1 to L4 that are suitable for BMD measurement by DXA.

    • Protocol compliance: Subject who, in the opinion of the investigator, is willing and able to comply with the requirements of the protocol.

    Exclusion:

    • T-Score: Has an absolute BMD value consistent with a T-score less than or equal to -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine.

    • Vertebral fractures: Has >1 prevalent vertebral fracture at the screening visit.

    • Non-vertebral fractures: Any previous non-vertebral osteoporosis related/fragility fracture after age 40.

    • Spine deformity: Significant spine deformity which would preclude DXA/QCT assessments.

    • BMI: BMI ≥33kg/m2.

    • Bone metabolic diseases: Other than osteoporosis, history or concurrent diseases affecting bone metabolism (e.g., osteomalacia, hyperparathyroidism, hyperthyroidism).

    • GI disease: History of major upper gastrointestinal disease

    • Malabsorption: Active or history of malabsorption (e.g., history of celiac disease, irritable bowel syndrome or inflammatory bowel disease).

    • Liver disease: Past or current history of liver disease or known hepatic or biliary abnormalities, (with the exception of previously documented diagnosis of Gilbert's syndrome).

    • Rheumatoid arthritis: Active disease or history of rheumatoid arthritis.

    • Nephrolithiasis: History of or active nephrolithiasis (kidney stones).

    • Osteosarcoma risk: Subjects at increased risk of osteosarcoma such as those with Paget's disease of bone or any prior external beam or implant radiation therapy involving the skeleton.

    • Malignancy: Malignant disease diagnosed within the previous 5 years (except resected basal cell cancer).

    • Biological abnormalities: Any clinically relevant biological abnormality found and/or volunteered at screening (other than those related to the disease under investigation) which, in the opinion of the investigator, is clinically significant and would preclude safe participation in this study.

    • Surgical and medical conditions: Presence of the following conditions within six months prior to screening: myocardial infarction, coronary bypass surgery, coronary artery angioplasty, unstable angina, cardiac arrhythmia, clinically evident congestive heart failure, or cerebrovascular accident.

    • Glomerular filtration rate: Glomerular filtration rate (GFR) <35 mL/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation as follows: GFR (mL/min/1.73 m2) = 186 x (Serum creatinine mg/dL)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American) (conventional units).

    • QT/QTc prolongation: A marked baseline prolongation of QT/QTc interval (e.g., QTc interval ≥450 msec on the Screening ECG).

    • Torsades de Pointes: A history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

    • Liver chemistries: Liver chemistries [aspartate aminotransferase (AST), alanine aminotransferase (ALT) or total bilirubin] exceeding 2-fold the upper limit of the laboratory-specified reference range, at screening.

    • Abnormal serum calcium: Serum calcium (total or albumin-adjusted) outside the central laboratory reference range at the screening visit.

    • Abnormal PTH: PTH (intact or whole) outside the normal range.

    • Abnormal creatine phosphokinase: Creatine phosphokinase (CPK) outside the normal range.

    • Abnormal alkaline phosphatase: Alkaline phosphatase outside of the normal range.

    • Thyroid hormone replacement: Subjects receiving thyroid hormone replacement therapy must have a TSH level checked. Subjects will be excluded if TSH levels are <0.1 or

    10.0mIU/L. However, subjects will not be excluded if TSH is in the range 0.1-4.5 mIU/L. If TSH is >4.5 and ≤10.0mIU/mL, measure T4 and exclude the subject only if the T4 is outside the normal range.

    • Vitamin D deficiency: Vitamin D deficiency (serum 25-hydroxy vitamin D < 20ng/mL, equivalent to 50nmol/L) at screening. Subjects can undergo vitamin D repletion as per local practice and be re-screened once only for vitamin D levels within the 6-week screening period. They will remain excluded if the re-screened value is < 20ng/mL.

    • Previous strontium or IV bisphosphonate: Any previous treatment with strontium ranelate or intravenous bisphosphonate.

    • Oral bisphosphonates: Any previous treatment with an oral bisphosphonate as follows:

    any treatment within the last six months

    • one month cumulative treatment within the last 12 months

    • three months cumulative treatment within the past two years, or

    • two years cumulative treatment within the past five years.

    • Fluoride: Treatment with fluoride (dose greater than 10mg/day) within the previous 5 years for osteoporosis.

    • Digoxin: Current therapy with digoxin.

    • Bone metabolism drugs: Treatment with other drugs affecting bone metabolism within the last six months prior to screening:

    Chronic systemic corticosteroid [e.g., glucocorticoid, mineralocorticoid] treatment of no more than 2 intra-articular injections within the past year or use of oral, parenteral, or long-term, high-dose inhaled corticosteroids. Treatment with any topical corticosteroid will not exclude the subject from participating.

    Hormones [e.g., estrogens/"natural estrogen preparations"(except for nonsystemic vaginal treatment), 19-norprogestins, SERMs such as raloxifene, anabolic steroids/androgens such as dehydroepiandrosterone (DHEA) or its sulfated form (DHEAS), nandrolone, tibolone, active vitamin D analogs/metabolites such as 1,25-dihydroxy vitamin D (calcitriol) or 1alpha-hydroxyvitamin D3 (1-alpha hydroxycholecalciferol), calcitonin].

    Calcineurin inhibitors [e.g., cyclosporine, tacrolimus] or methotrexate.

    • Previous anabolic agents: Treatment with PTH, PTH analogues or similar anabolic agent for osteoporosis within the last two years.

    • Contraindications: Contraindications to therapy with calcium or vitamin D.

    • Pregnancy: Women who are pregnant are not allowed in this study.

    • Interfering medications: Vitamin A in excess of 10,000 IU per day, heparin, or lithium, or anticonvulsant medications except benzodiazepines.

    • Investigational drug exposure: Administration of any investigational drug within 90 days preceding the first dose of the study drug.

    • Substance abuse: History or current evidence of drug or alcohol abuse within the previous 12 months.

    • Problems swallowing: Inability to swallow a tablet whole.

    The following exclusion criteria do not apply to subjects allocated to the open-label teriparatide group:

    • Calcium channel blockers: Current therapy with calcium channel blockers diltiazem and verapamil.

    • Oral Azole Antifungals: Current therapy with any oral azole antifungal.

    • Immunosuppressants: Current therapy with cyclosporine or oral tacrolimus.

    • Ritonavir: Current therapy with ritonavir.

    • Quinidine: Current therapy with quinidine.

    • Macrolide Antibiotics: Subjects anticipated to require chronic use of macrolide antibiotics.

    • Alendronate Contraindications: Contraindications to therapy with alendronate. Additional Exclusion Criteria for Subjects Recruited at QCT Sites

    • Hip surgery: History of hip surgery resulting in a metal implant on either the left or right side that would cause an artefact on a QCT scan.

    Additional Exclusion Criteria for Teriparatide Subjects

    • Teriparatide contraindications: Contraindications to therapy with teriparatide according to locally approved datasheet.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 GSK Investigational Site Oakland California United States 94609
    2 GSK Investigational Site Palm Desert California United States 92260
    3 GSK Investigational Site Walnut Creek California United States 94598
    4 GSK Investigational Site Decatur Georgia United States 30033
    5 GSK Investigational Site Bethesda Maryland United States 20817
    6 GSK Investigational Site Akron Ohio United States 44313
    7 GSK Investigational Site Cleveland Ohio United States 44195
    8 GSK Investigational Site Portland Oregon United States 97213
    9 GSK Investigational Site Duncansville Pennsylvania United States 16635
    10 GSK Investigational Site Ciudad Autónoma de Buenos Aires Buenos Aires Argentina C1117ABH
    11 GSK Investigational Site Ciudad Autonoma de Buenos Aires Argentina 1012
    12 GSK Investigational Site Ciudad Autónoma de Buenos Aires Argentina C1128AAF
    13 GSK Investigational Site St Leonards New South Wales Australia 2065
    14 GSK Investigational Site Footscray Victoria Australia 3011
    15 GSK Investigational Site Geelong Victoria Australia 3220
    16 GSK Investigational Site Heidelberg Victoria Australia 3081
    17 GSK Investigational Site Gent Belgium 9000
    18 GSK Investigational Site Liege Belgium 4020
    19 GSK Investigational Site Tienen Belgium 3300
    20 GSK Investigational Site Ballerup Denmark 2750
    21 GSK Investigational Site Frankfurt Hessen Germany 60528
    22 GSK Investigational Site Berlin Germany 10559
    23 GSK Investigational Site Berlin Germany 12203
    24 GSK Investigational Site Berlin Germany 12247
    25 GSK Investigational Site Berlin Germany 13125
    26 GSK Investigational Site Hamburg Germany 22143
    27 GSK Investigational Site Hamburg Germany 22415
    28 GSK Investigational Site Hong Kong Hong Kong
    29 GSK Investigational Site Shatin Hong Kong
    30 GSK Investigational Site Seoul Korea, Republic of 120-752
    31 GSK Investigational Site Suwon Korea, Republic of 443-721
    32 GSK Investigational Site Mexico, D.F. Mexico 14050
    33 GSK Investigational Site Bergen Norway 5094
    34 GSK Investigational Site Hamar Norway 2317
    35 GSK Investigational Site Oslo Norway 0176
    36 GSK Investigational Site Grudziadz Poland 86-300
    37 GSK Investigational Site Warszawa Poland 02-341
    38 GSK Investigational Site Wroclaw Poland 50-088
    39 GSK Investigational Site Moscow Russian Federation 117292
    40 GSK Investigational Site Moscow Russian Federation 127299
    41 GSK Investigational Site Panorama South Africa 7500
    42 GSK Investigational Site Rosebank South Africa 2196
    43 GSK Investigational Site Somerset West South Africa 7130
    44 GSK Investigational Site Barcelona Spain 08003
    45 GSK Investigational Site Barcelona Spain 08022
    46 GSK Investigational Site Madrid Spain 28007
    47 GSK Investigational Site Madrid Spain 28046
    48 GSK Investigational Site Santiago de Compostela Spain 15705
    49 GSK Investigational Site Santiago de Compostela Spain 15706

    Sponsors and Collaborators

    • GlaxoSmithKline

    Investigators

    • Study Director: GSK Clinical Trials, GlaxoSmithKline

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    GlaxoSmithKline
    ClinicalTrials.gov Identifier:
    NCT00471237
    Other Study ID Numbers:
    • CR9108963
    First Posted:
    May 9, 2007
    Last Update Posted:
    Nov 7, 2017
    Last Verified:
    Sep 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by GlaxoSmithKline
    bone mineral density,
    Ronacaleret
    teriparatide
    alendronate,
    Post-menopausal women,
    osteoporosis,
    SB-751689
    Additional relevant MeSH terms:
    Osteoporosis
    Alendronate
    Teriparatide

    Study Results

    Participant Flow

    Recruitment Details The study was conducted between 14-May-2007and 26-December-2008 at 45 centres in 14 countries.
    Pre-assignment Detail Of the 1609 participants screened, 1040 were screen failures, remaining 569 were randomized to the treatment arms. One participant from each of the 4 ronacaleret groups and alendronate group were excluded from Intent-to-Treat population and 564 participants were included in Intent-to-Treat population.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo once daily (OD) (matching to ronacaleret tablet) and matching placebo once weekly (OW) (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 milligrams (mg) and vitamin D, at least 400 international units (IU), OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 microgram (mcg), subcutaneous (SC) injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Period Title: Overall Study
    STARTED 90 87 82 88 87 89 41
    COMPLETED 49 45 48 43 46 50 38
    NOT COMPLETED 41 42 34 45 41 39 3

    Baseline Characteristics

    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD Total
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Total of all reporting groups
    Overall Participants 90 87 82 88 87 89 41 564
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    63.20
    (6.75)
    64.17
    (7.69)
    64.16
    (7.03)
    64.34
    (6.57)
    64.97
    (7.60)
    65.11
    (7.04)
    63.17
    (5.92)
    64.24
    (7.04)
    Sex: Female, Male (Count of Participants)
    Female
    90
    100%
    87
    100%
    82
    100%
    88
    100%
    87
    100%
    89
    100%
    41
    100%
    564
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Participant) [Number]
    African American/African Heritage
    1
    2
    1
    0
    4
    1
    0
    9
    American Indian or Alaska Native
    5
    5
    3
    3
    1
    4
    3
    24
    Asian
    10
    7
    10
    11
    10
    8
    3
    59
    White
    73
    71
    66
    73
    71
    76
    35
    465
    African American/African Heritage & White
    1
    2
    2
    1
    1
    0
    0
    7

    Outcome Measures

    1. Primary Outcome
    Title 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)
    Description 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.
    Time Frame Baseline (Day 0) and 12 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population comprised of any randomised or teriparatide participant who received at least one dose of study medication. Only those participants available at the specified time points were analyzed. Teriparatide arm was excluded from the analysis, since these participants were not randomized and were disproportionately represented.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 79 76 74 78 72 75
    Least Squares Mean (Standard Error) [Percent change in BMD]
    0.03
    (0.38)
    0.32
    (0.40)
    1.39
    (0.40)
    1.61
    (0.39)
    1.62
    (0.40)
    4.54
    (0.40)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.590
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.29
    Confidence Interval (2-Sided) 95%
    -0.78 to 1.37
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.55
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.36
    Confidence Interval (2-Sided) 95%
    0.28 to 2.44
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.55
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.58
    Confidence Interval (2-Sided) 95%
    0.51 to 2.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.54
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.60
    Confidence Interval (2-Sided) 95%
    0.51 to 2.69
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.55
    Estimation Comments
    2. Primary Outcome
    Title Number of Participants With Hypercalcemia
    Description 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.
    Time Frame Up to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Count of Participants [Participants]
    0
    0%
    1
    1.1%
    1
    1.2%
    4
    4.5%
    11
    12.6%
    0
    0%
    1
    2.4%
    3. Primary Outcome
    Title Number of Participants Withdrew Due to Hypercalcemia
    Description 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.
    Time Frame Up to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4. Primary Outcome
    Title Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
    Description 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.
    Time Frame Up to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Monocytes- high
    17
    18.9%
    14
    16.1%
    19
    23.2%
    17
    19.3%
    18
    20.7%
    28
    31.5%
    6
    14.6%
    Total neutrophils- high
    9
    10%
    11
    12.6%
    10
    12.2%
    10
    11.4%
    4
    4.6%
    6
    6.7%
    4
    9.8%
    Total neutrophils- low
    16
    17.8%
    5
    5.7%
    8
    9.8%
    8
    9.1%
    14
    16.1%
    13
    14.6%
    4
    9.8%
    Eosinophils- high
    12
    13.3%
    8
    9.2%
    11
    13.4%
    18
    20.5%
    19
    21.8%
    11
    12.4%
    6
    14.6%
    Glucose- high
    10
    11.1%
    6
    6.9%
    9
    11%
    5
    5.7%
    4
    4.6%
    5
    5.6%
    3
    7.3%
    Glucose- low
    3
    3.3%
    0
    0%
    4
    4.9%
    0
    0%
    3
    3.4%
    0
    0%
    0
    0%
    Basophils- high
    2
    2.2%
    0
    0%
    1
    1.2%
    0
    0%
    1
    1.1%
    1
    1.1%
    0
    0%
    Hematocrit- low
    2
    2.2%
    0
    0%
    0
    0%
    2
    2.3%
    0
    0%
    0
    0%
    1
    2.4%
    Hemoglobin- high
    1
    1.1%
    0
    0%
    1
    1.2%
    0
    0%
    1
    1.1%
    0
    0%
    1
    2.4%
    Hemoglobin- low
    2
    2.2%
    0
    0%
    0
    0%
    2
    2.3%
    1
    1.1%
    0
    0%
    1
    2.4%
    Platelets- high
    2
    2.2%
    0
    0%
    1
    1.2%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    White Blood Cell- high
    1
    1.1%
    0
    0%
    2
    2.4%
    0
    0%
    1
    1.1%
    0
    0%
    1
    2.4%
    White Blood Cell- low
    1
    1.1%
    1
    1.1%
    0
    0%
    2
    2.3%
    0
    0%
    0
    0%
    0
    0%
    Calcium- high
    0
    0%
    0
    0%
    1
    1.2%
    1
    1.1%
    1
    1.1%
    0
    0%
    0
    0%
    Phosphorus- high
    1
    1.1%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    1
    2.4%
    Alkaline Phosphatase- high
    0
    0%
    1
    1.1%
    0
    0%
    3
    3.4%
    3
    3.4%
    1
    1.1%
    0
    0%
    Total bilirubin- high
    0
    0%
    1
    1.1%
    2
    2.4%
    1
    1.1%
    1
    1.1%
    0
    0%
    0
    0%
    5. Primary Outcome
    Title Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
    Description 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.
    Time Frame Up to 12 Months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Systolic Blood Pressure, High
    5
    5.6%
    10
    11.5%
    8
    9.8%
    9
    10.2%
    11
    12.6%
    8
    9%
    1
    2.4%
    Systolic Blood Pressure, Low
    6
    6.7%
    8
    9.2%
    10
    12.2%
    6
    6.8%
    4
    4.6%
    8
    9%
    3
    7.3%
    Diastolic Blood Pressure, High
    2
    2.2%
    6
    6.9%
    5
    6.1%
    1
    1.1%
    6
    6.9%
    3
    3.4%
    1
    2.4%
    Diastolic Blood Pressure, Low
    8
    8.9%
    9
    10.3%
    4
    4.9%
    12
    13.6%
    10
    11.5%
    10
    11.2%
    2
    4.9%
    Heart Rate, Low
    2
    2.2%
    0
    0%
    1
    1.2%
    1
    1.1%
    1
    1.1%
    0
    0%
    0
    0%
    6. Primary Outcome
    Title Number of Participant With Electrocardiogram (ECG) Findings Reported as Adverse Event
    Description 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.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Count of Participants [Participants]
    1
    1.1%
    5
    5.7%
    4
    4.9%
    3
    3.4%
    3
    3.4%
    5
    5.6%
    0
    0%
    7. Primary Outcome
    Title Mean Change From Baseline in Height
    Description 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.
    Time Frame Baseline (Day 0), Month 6, 12 and early withdrawal

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Month 6
    -0.04
    (0.58)
    0.17
    (1.41)
    0.72
    (3.82)
    0.05
    (0.70)
    -0.04
    (0.82)
    -0.07
    (1.13)
    0.11
    (0.65)
    Month 12
    -0.14
    (0.65)
    0.04
    (1.59)
    0.02
    (0.76)
    -0.09
    (1.04)
    -0.17
    (0.67)
    -0.08
    (0.57)
    0.11
    (0.56)
    Early withdrawal
    0.03
    (0.61)
    0.17
    (1.92)
    -0.13
    (0.55)
    -0.16
    (0.76)
    -0.16
    (0.82)
    -0.37
    (0.88)
    0
    (0)
    8. Primary Outcome
    Title Mean Change From Baseline in Weight
    Description 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.
    Time Frame Baseline (Day 0), Month 6, 12 and early withdrawal

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Month 6
    -0.02
    (2.12)
    0.27
    (3.27)
    0.45
    (2.98)
    -0.24
    (2.87)
    0.11
    (2.84)
    0.29
    (1.89)
    0.51
    (1.84)
    Month 12
    0.32
    (2.73)
    -0.72
    (2.70)
    1.18
    (9.78)
    -0.22
    (2.36)
    -0.48
    (2.28)
    0.57
    (3.22)
    0.09
    (2.45)
    Early withdrawal
    -0.45
    (2.40)
    0.40
    (4.60)
    -0.34
    (2.48)
    0.37
    (3.86)
    0.00
    (2.17)
    -0.12
    (2.33)
    -2.15
    (1.48)
    9. Secondary Outcome
    Title Percent Change From Baseline to Month 6 in BMD Measured by DXA Scans of the Lumbar Spine (L1-L4)
    Description 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.
    Time Frame Baseline (Day 0) and Month 6

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat Population. Only those participants available at the specified time point were analyzed. Participants from Teriparatide, 20 mcg, SC injection, OD arm were excluded from the analysis, since these participants were not randomized and were disproportionately represented.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 79 76 74 77 73 75
    Least Squares Mean (Standard Error) [percent change in BMD]
    0.66
    (0.33)
    0.21
    (0.34)
    1.61
    (0.35)
    0.47
    (0.34)
    1.01
    (0.35)
    3.42
    (0.34)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.680
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.45
    Confidence Interval (2-Sided) 95%
    -1.38 to 0.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.192
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.01 to 1.89
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.48
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.680
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -1.12 to 0.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.47
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.680
    Comments
    Method ANOVA
    Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.35
    Confidence Interval (2-Sided) 95%
    -0.59 to 1.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.48
    Estimation Comments
    10. Secondary Outcome
    Title Percent Change From Baseline to Months 6 and 12 in BMD Measured by DXA Scans of the Hip (Total Hip, Femoral Neck and Trochanter).
    Description 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.
    Time Frame Baseline (Day 0), Month 6 and Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed. Participants from Teriparatide, 20 mcg, SC injection, OD arm were excluded from the analysis, since these participants were not randomized and were disproportionately represented.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89
    Total Hip aBMD, Month 6
    0.42
    (0.23)
    -0.26
    (0.24)
    -0.37
    (0.24)
    -0.86
    (0.23)
    -0.88
    (0.24)
    1.84
    (0.24)
    Total Hip aBMD, Month 12
    0.27
    (0.26)
    -0.62
    (0.26)
    -0.75
    (0.27)
    -1.07
    (0.26)
    -1.31
    (0.27)
    2.70
    (0.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
    Comments Total Hip aBMD, Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.037
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.68
    Confidence Interval (2-Sided) 95%
    -1.32 to -0.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
    Comments Total Hip aBMD, Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.79
    Confidence Interval (2-Sided) 95%
    -1.43 to -0.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
    Comments Total Hip aBMD, Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.000
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.28
    Confidence Interval (2-Sided) 95%
    -1.92 to -0.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
    Comments Total Hip aBMD, Month 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.000
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.30
    Confidence Interval (2-Sided) 95%
    -1.95 to -0.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
    Comments Total Hip aBMD, Month 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.89
    Confidence Interval (2-Sided) 95%
    -1.61 to -0.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.36
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
    Comments Total Hip aBMD, Month 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -1.74 to -0.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
    Comments Total Hip aBMD, Month 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.000
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.33
    Confidence Interval (2-Sided) 95%
    -2.04 to -0.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.36
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
    Comments Total Hip aBMD, Month 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.000
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Median Difference (Net)
    Estimated Value -1.57
    Confidence Interval (2-Sided) 95%
    -2.30 to -0.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments
    11. Secondary Outcome
    Title Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
    Description 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%.
    Time Frame Baseline (Day 0), Month 5, 6 and 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Month 5, Vertebra, BMD % change >=0
    0
    0%
    0
    0%
    1
    1.2%
    0
    0%
    1
    1.1%
    0
    0%
    0
    0%
    Month 5, Femur, BMD % change >=0
    0
    0%
    0
    0%
    1
    1.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Month 5, Vertebra + Femur, BMD % change >=0
    0
    0%
    0
    0%
    1
    1.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Month 6, Vertebra, BMD % change >=0
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    Month 6, Femur, BMD % change >=0
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    Month 6, Vertebra + Femur, BMD % change >=0
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    0
    0%
    Month 12, Vertebra, BMD % change >=0
    16
    17.8%
    29
    33.3%
    32
    39%
    35
    39.8%
    31
    35.6%
    44
    49.4%
    34
    82.9%
    Month 12, Femur, BMD % change >=0
    20
    22.2%
    23
    26.4%
    14
    17.1%
    19
    21.6%
    16
    18.4%
    40
    44.9%
    25
    61%
    Month 12, Vertebra + Femur, BMD % change >=0
    10
    11.1%
    19
    21.8%
    12
    14.6%
    17
    19.3%
    16
    18.4%
    35
    39.3%
    24
    58.5%
    Early Withdrawal, Vertebra, BMD % change >=0
    1
    1.1%
    1
    1.1%
    1
    1.2%
    2
    2.3%
    1
    1.1%
    0
    0%
    1
    2.4%
    Early Withdrawal, Femur, BMD % change >=0
    1
    1.1%
    1
    1.1%
    0
    0%
    1
    1.1%
    1
    1.1%
    0
    0%
    1
    2.4%
    Early Withdrawal, Vertebra + Femur, BMD %change>=0
    1
    1.1%
    1
    1.1%
    0
    0%
    1
    1.1%
    1
    1.1%
    0
    0%
    1
    2.4%
    12. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Baseline (Day 0) and Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Total vertebra integral VOI BMD
    -0.98
    (3.13)
    1.09
    (4.01)
    3.00
    (4.98)
    3.91
    (4.98)
    4.83
    (6.56)
    5.04
    (4.39)
    14.80
    (8.69)
    Mid vertebra integral VOI BMD
    -1.31
    (3.54)
    1.20
    (4.85)
    4.65
    (5.87)
    6.06
    (6.48)
    7.33
    (8.67)
    4.85
    (5.25)
    17.97
    (11.27)
    Mid Cylinder trabecular VOI BMD
    -2.45
    (4.39)
    1.75
    (8.70)
    6.17
    (10.37)
    8.99
    (10.52)
    13.29
    (15.32)
    4.88
    (7.68)
    24.37
    (15.92)
    Mid Osteo trabecular VOI BMD
    -2.21
    (4.58)
    1.81
    (8.26)
    7.06
    (9.25)
    9.54
    (9.79)
    13.21
    (14.68)
    5.15
    (6.86)
    24.21
    (15.80)
    Total vertebra trabecular VOI BMD
    -2.46
    (4.58)
    1.67
    (7.18)
    5.81
    (8.31)
    8.52
    (8.97)
    11.40
    (12.83)
    4.97
    (6.43)
    23.82
    (14.64)
    Mid Osteo cortical VOI BMD
    -0.30
    (4.69)
    0.63
    (4.80)
    2.37
    (6.37)
    2.57
    (5.14)
    1.22
    (4.39)
    4.98
    (4.63)
    9.25
    (7.68)
    13. Secondary Outcome
    Title Percent Change From Baseline to Month 12 in the Total Vertebra Integral VOI at the Lumbar Spine as Measured by QCT Scans
    Description 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%.
    Time Frame Baseline (Day 0) and Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 42 50 43 43 41 49 36
    Mean (Standard Deviation) [Percent change in VOI]
    0.04
    (4.19)
    0.85
    (4.14)
    3.01
    (5.18)
    3.58
    (5.70)
    3.54
    (5.64)
    5.39
    (5.87)
    12.23
    (8.43)
    14. Secondary Outcome
    Title Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
    Description 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%.
    Time Frame Baseline (Day 0) and Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 41 47 40 39 37 45 26
    Femur integral VOI BMD
    0.02
    (2.78)
    -0.05
    (2.67)
    -0.81
    (2.80)
    -0.53
    (2.18)
    -0.15
    (2.98)
    2.70
    (2.13)
    3.92
    (2.67)
    Femur trabecular VOI BMD
    -0.36
    (5.53)
    -0.40
    (6.81)
    -2.16
    (7.39)
    1.16
    (5.06)
    2.81
    (8.20)
    3.05
    (5.92)
    13.19
    (8.96)
    Femur cortical VOI BMD
    1.11
    (4.04)
    -0.32
    (2.90)
    -1.46
    (2.81)
    -1.06
    (2.53)
    -1.79
    (3.01)
    2.44
    (3.13)
    0.22
    (2.63)
    Neck integral VOI BMD
    -0.10
    (2.48)
    0.16
    (2.83)
    -0.94
    (3.34)
    -1.20
    (2.99)
    -1.45
    (3.22)
    1.65
    (2.72)
    2.06
    (3.65)
    Neck trabecular VOI BMD
    -0.95
    (7.44)
    -2.19
    (7.91)
    -2.68
    (6.14)
    1.35
    (9.91)
    3.05
    (11.18)
    2.77
    (7.55)
    11.27
    (10.31)
    Neck cortical VOI BMD
    1.23
    (4.55)
    0.44
    (4.16)
    -1.67
    (3.95)
    -1.85
    (3.89)
    -2.80
    (4.55)
    1.10
    (4.25)
    -0.69
    (4.49)
    Trochanter integral VOI BMD
    -0.58
    (3.88)
    -0.16
    (4.22)
    -1.53
    (3.92)
    -1.16
    (3.29)
    -0.98
    (3.83)
    3.15
    (3.27)
    4.96
    (4.74)
    Trochanter trabecular VOI BMD
    -1.62
    (9.67)
    -1.34
    (13.50)
    -2.54
    (11.05)
    2.12
    (8.82)
    2.10
    (10.66)
    3.55
    (7.55)
    14.12
    (14.51)
    Trochanter cortical VOI BMD
    0.56
    (5.29)
    -0.70
    (4.08)
    -1.53
    (3.60)
    -1.48
    (3.53)
    -2.59
    (4.04)
    3.33
    (3.57)
    1.99
    (4.37)
    15. Secondary Outcome
    Title Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans
    Description 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%.
    Time Frame Baseline (Day 0) and Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 41 47 40 39 37 45 26
    Neck cortical VOI Thickness
    -0.85
    (7.09)
    -0.13
    (5.98)
    1.12
    (5.75)
    -0.88
    (4.73)
    0.32
    (4.93)
    -0.13
    (5.98)
    0.39
    (4.36)
    Trochanter cortical VOI Thickness
    -1.00
    (5.85)
    0.76
    (4.40)
    1.01
    (5.15)
    -0.82
    (3.65)
    1.60
    (3.70)
    0.81
    (5.39)
    0.76
    (2.93)
    16. Secondary Outcome
    Title Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
    Description Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of CTX1.
    Time Frame Baseline (Day 0), Week 4, Month 3, 6, and 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Baseline
    625.2
    (1.05)
    635.3
    (1.05)
    632.0
    (1.05)
    587.9
    (1.05)
    645.5
    (1.05)
    630.4
    (1.05)
    564.0
    (1.07)
    Baseline, Placebo contrast
    1.02
    (1.07)
    1.01
    (1.07)
    0.94
    (1.07)
    1.03
    (1.07)
    1.01
    (1.07)
    0.90
    (1.09)
    Week 4
    530.7
    (1.05)
    515.2
    (1.05)
    525.4
    (1.05)
    506.1
    (1.05)
    529.2
    (1.05)
    288.0
    (1.06)
    576.1
    (1.08)
    Week 4, Placebo contrast
    0.97
    (1.08)
    0.99
    (1.08)
    0.95
    (1.08)
    1.00
    (1.08)
    0.54
    (1.08)
    1.09
    (1.10)
    Month 3
    523.5
    (1.05)
    598.5
    (1.06)
    688.9
    (1.06)
    723.2
    (1.05)
    818.9
    (1.06)
    257.1
    (1.06)
    864.1
    (1.08)
    Month 3, Placebo contrast
    1.14
    (1.08)
    1.32
    (1.08)
    1.38
    (1.08)
    1.56
    (1.08)
    0.49
    (1.08)
    1.65
    (1.10)
    Month 6
    517.6
    (1.06)
    648.2
    (1.06)
    777.1
    (1.06)
    859.6
    (1.06)
    964.3
    (1.06)
    235.9
    (1.07)
    1112
    (1.08)
    Month 6, Placebo contrast
    1.25
    (1.08)
    1.50
    (1.08)
    1.66
    (1.08)
    1.86
    (1.08)
    0.46
    (1.09)
    2.15
    (1.10)
    Month 12
    525.1
    (1.08)
    695.2
    (1.08)
    806.1
    (1.08)
    852.8
    (1.08)
    991.9
    (1.08)
    158.3
    (1.08)
    1071
    (1.10)
    Month 12, Placebo contrast
    1.32
    (1.12)
    1.54
    (1.11)
    1.62
    (1.12)
    1.89
    (1.11)
    0.30
    (1.11)
    2.04
    (1.13)
    17. Secondary Outcome
    Title Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
    Description Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of P1NP.
    Time Frame Baseline (Day 0), Week 4, Month 3, 6, and 12

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Baseline
    47.66
    (1.05)
    45.59
    (1.05)
    47.70
    (1.05)
    46.62
    (1.05)
    46.19
    (1.05)
    47.71
    (1.05)
    48.57
    (1.07)
    Baseline, Placebo contrast
    0.96
    (1.07)
    1.00
    (1.07)
    0.98
    (1.07)
    0.97
    (1.07)
    1.00
    (1.07)
    1.02
    (1.08)
    Week 4
    45.32
    (1.05)
    49.67
    (1.05)
    57.36
    (1.05)
    60.27
    (1.05)
    63.46
    (1.05)
    43.66
    (1.05)
    92.74
    (1.07)
    Week 4, Placebo contrast
    1.10
    (1.07)
    1.27
    (1.07)
    1.33
    (1.07)
    1.40
    (1.07)
    0.96
    (1.07)
    2.05
    (1.09)
    Month 3
    39.53
    (1.05)
    49.99
    (1.05)
    65.21
    (1.05)
    73.68
    (1.05)
    86.84
    (1.05)
    20.15
    (1.05)
    99.74
    (1.08)
    Month 3, Placebo contrast
    1.26
    (1.08)
    1.65
    (1.08)
    1.86
    (1.08)
    2.20
    (1.08)
    0.51
    (1.07)
    2.52
    (1.09)
    Month 6
    38.41
    (1.05)
    56.37
    (1.05)
    75.73
    (1.06)
    90.55
    (1.05)
    104.6
    (1.05)
    16.41
    (1.05)
    117.8
    (1.08)
    Month 6, Placebo contrast
    1.47
    (1.08)
    1.97
    (1.08)
    2.36
    (1.08)
    2.72
    (1.08)
    0.43
    (1.08)
    3.07
    (1.09)
    Month 12
    40.74
    (1.05)
    61.43
    (1.05)
    82.69
    (1.05)
    98.04
    (1.05)
    112.6
    (1.05)
    16.98
    (1.05)
    119.0
    (1.07)
    Month 12, Placebo contrast
    1.51
    (1.08)
    2.03
    (1.08)
    2.41
    (1.08)
    2.76
    (1.08)
    0.42
    (1.08)
    2.92
    (1.09)
    18. Secondary Outcome
    Title Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
    Description Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of BALP.
    Time Frame Baseline (Day 0), Week 4, Month 3, 6, and 12

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 90 87 82 88 87 89 41
    Baseline
    14.46
    (1.04)
    14.96
    (1.04)
    14.24
    (1.04)
    15.06
    (1.04)
    14.12
    (1.04)
    14.31
    (1.04)
    14.50
    (1.05)
    Baseline, Placebo contrast
    1.03
    (1.05)
    0.98
    (1.05)
    1.04
    (1.05)
    0.98
    (1.05)
    0.99
    (1.05)
    1.00
    (1.07)
    Week 4
    14.02
    (1.04)
    14.72
    (1.04)
    14.51
    (1.04)
    15.97
    (1.04)
    15.72
    (1.04)
    13.68
    (1.04)
    16.19
    (1.06)
    Week 4, Placebo contrast
    1.05
    (1.05)
    1.03
    (1.06)
    1.14
    (1.05)
    1.12
    (1.05)
    0.98
    (1.05)
    1.15
    (1.07)
    Month 3
    12.66
    (1.04)
    15.23
    (1.04)
    15.44
    (1.04)
    18.77
    (1.04)
    17.85
    (1.04)
    9.44
    (1.04)
    16.53
    (1.06)
    Month 3, Placebo contrast
    1.20
    (1.06)
    1.22
    (1.06)
    1.48
    (1.06)
    1.41
    (1.06)
    0.75
    (1.06)
    1.31
    (1.07)
    Month 6
    12.81
    (1.04)
    16.31
    (1.04)
    17.43
    (1.04)
    22.18
    (1.04)
    21.47
    (1.04)
    8.36
    (1.04)
    17.63
    (1.06)
    Month 6, Placebo contrast
    1.27
    (1.06)
    1.36
    (1.06)
    1.73
    (1.06)
    1.68
    (1.06)
    0.65
    (1.06)
    1.38
    (1.07)
    Month 12
    13.25
    (1.04)
    16.64
    (1.04)
    18.80
    (1.04)
    23.36
    (1.04)
    23.28
    (1.04)
    8.42
    (1.04)
    19.08
    (1.06)
    Month 12, Placebo contrast
    1.26
    (1.06)
    1.42
    (1.06)
    1.76
    (1.06)
    1.76
    (1.06)
    0.64
    (1.06)
    1.44
    (1.07)
    19. Secondary Outcome
    Title Blood Concentrations of Ronacaleret
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Concentration Population comprised of any Intent-to-Treat participants for whom a SB-751689 pharmacokinetic blood sample was obtained and analyzed. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
    Arm/Group Description Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 76 74 80 78
    Week 4, Pre-dose
    41.22
    (127.438)
    37.24
    (36.203)
    85.44
    (158.849)
    79.40
    (74.083)
    Week 4, 8-12 h post dose
    204.82
    (183.245)
    328.33
    (222.061)
    581.08
    (360.031)
    685.14
    (450.467)
    Month 6, Pre-dose
    21.37
    (19.769)
    65.94
    (214.325)
    74.12
    (146.094)
    117.94
    (288.413)
    Month 6, 1-4 h post dose
    644.90
    (408.282)
    1308.35
    (943.397)
    1610.74
    (1016.608)
    2054.71
    (1499.079)
    Month 6, 8-12 h post dose
    186.69
    (101.326)
    385.03
    (284.963)
    576.35
    (382.494)
    796.99
    (640.016)
    Month 6, 24 h post dose
    186.21
    (151.855)
    290.74
    (125.486)
    578.63
    (398.915)
    473.41
    (237.671)
    Month 12, Pre-dose
    20.68
    (15.971)
    33.47
    (26.747)
    147.63
    (370.860)
    114.83
    (179.448)
    Month 12, 1-4 h post dose
    779.92
    (465.356)
    999.63
    (659.880)
    1819.53
    (1021.984)
    2128.24
    (1549.003)
    Month 12, 8-12 h post dose
    203.39
    (124.866)
    262.20
    (137.152)
    651.95
    (391.752)
    740.18
    (679.348)
    Month 12, 24 h post dose
    187.23
    (100.001)
    297.20
    (146.806)
    626.72
    (231.777)
    512.65
    (314.692)
    20. Secondary Outcome
    Title 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
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Parameters Population comprised of any participant in the pharmacokinetic concentration population who provided pharmacokinetic parameters. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
    Arm/Group Description Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 13 14 14 11
    AUC 0-t, Month 6
    2495.8751
    (53.13)
    4575.8746
    (35.50)
    7545.3302
    (42.26)
    6712.0537
    (79.69)
    AUC 0-t, Month 12
    2766.6822
    (64.20)
    4548.6490
    (43.87)
    9259.3127
    (37.74)
    6798.4219
    (65.17)
    AUC 0-tau, Month 6
    3628.0901
    (66.72)
    6428.5540
    (36.62)
    10825.9083
    (50.48)
    9810.4614
    (80.08)
    AUC 0-tau, Month 12
    3922.9369
    (75.72)
    6455.1756
    (42.03)
    14827.6940
    (38.28)
    10079.2847
    (71.01)
    21. Secondary Outcome
    Title Maximum Blood Concentration (Cmax) of Ronacaleret
    Description 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 Frame 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameter population.
    Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
    Arm/Group Description Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 13 14 14 11
    Cmax. Month 6
    572.10
    (44.79)
    1050.42
    (40.82)
    1756.45
    (52.80)
    1556.58
    (76.83)
    Cmax. Month 12
    661.70
    (74.39)
    999.91
    (37.18)
    2254.26
    (41.57)
    1506.45
    (63.78)
    22. Secondary Outcome
    Title Time Required to Achieve Maximum Concentration of Ronacaleret in Blood (Tmax)
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters population. Only those participants available at the specified time points were analyzed.
    Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
    Arm/Group Description Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    Measure Participants 13 14 14 11
    Tmax, Month 6
    1.483
    1.250
    1.700
    1.500
    Tmax, Month 12
    1.000
    1.500
    1.500
    1.500

    Adverse Events

    Time Frame Up to Follow-up visit (12 month and 2 weeks)
    Adverse Event Reporting Description Intent-to-Treat population was used to report AEs
    Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
    All Cause Mortality
    Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Serious Adverse Events
    Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/90 (0%) 2/87 (2.3%) 5/82 (6.1%) 7/88 (8%) 3/87 (3.4%) 6/89 (6.7%) 4/41 (9.8%)
    Cardiac disorders
    Acute myocardial infarction 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Arrhythmia 0/90 (0%) 1/87 (1.1%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Atrioventricular block 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Myocardial infarction 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 1/89 (1.1%) 0/41 (0%)
    Gastrointestinal disorders
    Inguinal hernia 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Upper gastrointestinal haemorrhage 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 1/87 (1.1%) 0/89 (0%) 0/41 (0%)
    General disorders
    Chest pain 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 1/41 (2.4%)
    Hyperplasia 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 1/41 (2.4%)
    Infections and infestations
    Appendicitis 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 1/87 (1.1%) 0/89 (0%) 0/41 (0%)
    Infection 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 1/89 (1.1%) 0/41 (0%)
    Pulmonary tuberculosis 0/90 (0%) 0/87 (0%) 1/82 (1.2%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Injury, poisoning and procedural complications
    Femoral neck fracture 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 1/89 (1.1%) 0/41 (0%)
    Femur fracture 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 1/89 (1.1%) 0/41 (0%)
    Nerve injury 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 1/41 (2.4%)
    Radius fracture 0/90 (0%) 1/87 (1.1%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Upper limb fracture 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 1/87 (1.1%) 0/89 (0%) 0/41 (0%)
    Investigations
    Smear cervix abnormal 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 1/41 (2.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastatic malignant melanoma 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Neuroma 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Non-Hodgkin's lymphoma 0/90 (0%) 0/87 (0%) 1/82 (1.2%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Renal neoplasm 0/90 (0%) 0/87 (0%) 1/82 (1.2%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Nervous system disorders
    Loss of consciousness 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Syncope 0/90 (0%) 0/87 (0%) 1/82 (1.2%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Transient ischaemic attack 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 1/41 (2.4%)
    Reproductive system and breast disorders
    Cystocele 0/90 (0%) 0/87 (0%) 1/82 (1.2%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Ovarian cyst 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 1/89 (1.1%) 0/41 (0%)
    Respiratory, thoracic and mediastinal disorders
    Nasal septum deviation 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 0/89 (0%) 1/41 (2.4%)
    Surgical and medical procedures
    Salpingo-oophorectomy 0/90 (0%) 0/87 (0%) 0/82 (0%) 0/88 (0%) 0/87 (0%) 1/89 (1.1%) 0/41 (0%)
    Vascular disorders
    Hypertension 0/90 (0%) 0/87 (0%) 0/82 (0%) 1/88 (1.1%) 0/87 (0%) 0/89 (0%) 0/41 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 54/90 (60%) 54/87 (62.1%) 57/82 (69.5%) 55/88 (62.5%) 61/87 (70.1%) 46/89 (51.7%) 30/41 (73.2%)
    Cardiac disorders
    Palpitations 1/90 (1.1%) 1/87 (1.1%) 0/82 (0%) 4/88 (4.5%) 2/87 (2.3%) 1/89 (1.1%) 3/41 (7.3%)
    Gastrointestinal disorders
    Diarrhoea 5/90 (5.6%) 6/87 (6.9%) 8/82 (9.8%) 11/88 (12.5%) 12/87 (13.8%) 5/89 (5.6%) 1/41 (2.4%)
    Nausea 4/90 (4.4%) 1/87 (1.1%) 6/82 (7.3%) 9/88 (10.2%) 11/87 (12.6%) 6/89 (6.7%) 2/41 (4.9%)
    Dyspepsia 4/90 (4.4%) 6/87 (6.9%) 3/82 (3.7%) 6/88 (6.8%) 3/87 (3.4%) 4/89 (4.5%) 3/41 (7.3%)
    Constipation 2/90 (2.2%) 5/87 (5.7%) 4/82 (4.9%) 9/88 (10.2%) 5/87 (5.7%) 2/89 (2.2%) 0/41 (0%)
    Abdominal pain upper 6/90 (6.7%) 3/87 (3.4%) 6/82 (7.3%) 4/88 (4.5%) 1/87 (1.1%) 1/89 (1.1%) 0/41 (0%)
    Abdominal pain 0/90 (0%) 5/87 (5.7%) 0/82 (0%) 3/88 (3.4%) 2/87 (2.3%) 1/89 (1.1%) 0/41 (0%)
    Infections and infestations
    Nasopharyngitis 17/90 (18.9%) 16/87 (18.4%) 13/82 (15.9%) 12/88 (13.6%) 16/87 (18.4%) 12/89 (13.5%) 7/41 (17.1%)
    Influenza 7/90 (7.8%) 6/87 (6.9%) 5/82 (6.1%) 6/88 (6.8%) 9/87 (10.3%) 7/89 (7.9%) 4/41 (9.8%)
    Upper respiratory tract infection 5/90 (5.6%) 5/87 (5.7%) 4/82 (4.9%) 2/88 (2.3%) 8/87 (9.2%) 3/89 (3.4%) 2/41 (4.9%)
    Bronchitis 5/90 (5.6%) 4/87 (4.6%) 3/82 (3.7%) 4/88 (4.5%) 1/87 (1.1%) 2/89 (2.2%) 1/41 (2.4%)
    Urinary tract infection 3/90 (3.3%) 4/87 (4.6%) 6/82 (7.3%) 0/88 (0%) 3/87 (3.4%) 1/89 (1.1%) 2/41 (4.9%)
    Gastroenteritis 2/90 (2.2%) 5/87 (5.7%) 0/82 (0%) 1/88 (1.1%) 2/87 (2.3%) 2/89 (2.2%) 4/41 (9.8%)
    Tooth infection 1/90 (1.1%) 2/87 (2.3%) 0/82 (0%) 4/88 (4.5%) 0/87 (0%) 2/89 (2.2%) 3/41 (7.3%)
    Injury, poisoning and procedural complications
    Fall 1/90 (1.1%) 0/87 (0%) 3/82 (3.7%) 2/88 (2.3%) 5/87 (5.7%) 1/89 (1.1%) 0/41 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/90 (5.6%) 7/87 (8%) 9/82 (11%) 5/88 (5.7%) 10/87 (11.5%) 7/89 (7.9%) 5/41 (12.2%)
    Back pain 10/90 (11.1%) 6/87 (6.9%) 2/82 (2.4%) 6/88 (6.8%) 6/87 (6.9%) 5/89 (5.6%) 3/41 (7.3%)
    Pain in extremity 3/90 (3.3%) 3/87 (3.4%) 2/82 (2.4%) 0/88 (0%) 4/87 (4.6%) 3/89 (3.4%) 4/41 (9.8%)
    Muscle spasms 2/90 (2.2%) 5/87 (5.7%) 2/82 (2.4%) 2/88 (2.3%) 1/87 (1.1%) 0/89 (0%) 4/41 (9.8%)
    Osteoarthritis 3/90 (3.3%) 2/87 (2.3%) 1/82 (1.2%) 1/88 (1.1%) 1/87 (1.1%) 5/89 (5.6%) 0/41 (0%)
    Nervous system disorders
    Headache 7/90 (7.8%) 5/87 (5.7%) 5/82 (6.1%) 4/88 (4.5%) 4/87 (4.6%) 8/89 (9%) 6/41 (14.6%)
    Dizziness 4/90 (4.4%) 5/87 (5.7%) 8/82 (9.8%) 5/88 (5.7%) 10/87 (11.5%) 0/89 (0%) 6/41 (14.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/90 (5.6%) 4/87 (4.6%) 3/82 (3.7%) 2/88 (2.3%) 2/87 (2.3%) 2/89 (2.2%) 0/41 (0%)
    Vascular disorders
    Hypertension 4/90 (4.4%) 5/87 (5.7%) 5/82 (6.1%) 2/88 (2.3%) 3/87 (3.4%) 3/89 (3.4%) 2/41 (4.9%)

    Limitations/Caveats

    The study was terminated for futility in a phased manner by the sponsor on 25-Sep-2008 once the results of a planned 6-month interim analysis were available.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

    Results Point of Contact

    Name/Title GSK Response Center
    Organization GlaxoSmithKline
    Phone 866-435-7343
    Email
    Responsible Party:
    GlaxoSmithKline
    ClinicalTrials.gov Identifier:
    NCT00471237
    Other Study ID Numbers:
    • CR9108963
    First Posted:
    May 9, 2007
    Last Update Posted:
    Nov 7, 2017
    Last Verified:
    Sep 1, 2017