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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00471237




Registration number
NCT00471237
Ethics application status
Date submitted
7/05/2007
Date registered
9/05/2007

Titles & IDs
Public title
A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis.
Scientific 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
Secondary ID [1] 0 0
CR9108963
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ronacaleret
Treatment: Drugs - Teriparatide
Treatment: Drugs - Alendronate

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

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

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.


Treatment: Drugs: Ronacaleret
100mg, 200mg, 300mg, 400mg

Treatment: Drugs: Teriparatide
PTH (1-34)

Treatment: Drugs: Alendronate
Bisphosphonate

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Baseline (Day 0) and 12 Months
Primary outcome [2] 0 0
Number of Participants With Hypercalcemia
Timepoint [2] 0 0
Up to Month 12
Primary outcome [3] 0 0
Number of Participants Withdrew Due to Hypercalcemia
Timepoint [3] 0 0
Up to Month 12
Primary outcome [4] 0 0
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Timepoint [4] 0 0
Up to Month 12
Primary outcome [5] 0 0
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Timepoint [5] 0 0
Up to 12 Months
Primary outcome [6] 0 0
Number of Participant With Electrocardiogram (ECG) Findings Reported as Adverse Event
Timepoint [6] 0 0
Up to 12 months
Primary outcome [7] 0 0
Mean Change From Baseline in Height
Timepoint [7] 0 0
Baseline (Day 0), Month 6, 12 and early withdrawal
Primary outcome [8] 0 0
Mean Change From Baseline in Weight
Timepoint [8] 0 0
Baseline (Day 0), Month 6, 12 and early withdrawal
Secondary outcome [1] 0 0
Percent Change From Baseline to Month 6 in BMD Measured by DXA Scans of the Lumbar Spine (L1-L4)
Timepoint [1] 0 0
Baseline (Day 0) and Month 6
Secondary outcome [2] 0 0
Percent Change From Baseline to Months 6 and 12 in BMD Measured by DXA Scans of the Hip (Total Hip, Femoral Neck and Trochanter).
Timepoint [2] 0 0
Baseline (Day 0), Month 6 and Month 12
Secondary outcome [3] 0 0
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Timepoint [3] 0 0
Baseline (Day 0), Month 5, 6 and 12
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline (Day 0) and Month 12
Secondary outcome [5] 0 0
Percent Change From Baseline to Month 12 in the Total Vertebra Integral VOI at the Lumbar Spine as Measured by QCT Scans
Timepoint [5] 0 0
Baseline (Day 0) and Month 12
Secondary outcome [6] 0 0
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Timepoint [6] 0 0
Baseline (Day 0) and Month 12
Secondary outcome [7] 0 0
Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans
Timepoint [7] 0 0
Baseline (Day 0) and Month 12
Secondary outcome [8] 0 0
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide a1 Chain of Type 1 Collagen (CTX1)
Timepoint [8] 0 0
Baseline (Day 0), Week 4, Month 3, 6, and 12
Secondary outcome [9] 0 0
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Timepoint [9] 0 0
Baseline (Day 0), Week 4, Month 3, 6, and 12
Secondary outcome [10] 0 0
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Timepoint [10] 0 0
Baseline (Day 0), Week 4, Month 3, 6, and 12
Secondary outcome [11] 0 0
Blood Concentrations of Ronacaleret
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Maximum Blood Concentration (Cmax) of Ronacaleret
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
Time Required to Achieve Maximum Concentration of Ronacaleret in Blood (Tmax)
Timepoint [14] 0 0
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

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
79 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - St Leonards
Recruitment hospital [2] 0 0
GSK Investigational Site - Footscray
Recruitment hospital [3] 0 0
GSK Investigational Site - Geelong
Recruitment hospital [4] 0 0
GSK Investigational Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
3011 - Footscray
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
3081 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
Ciudad Autonoma de Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
Ciudad Autónoma de Buenos Aires
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Belgium
State/province [11] 0 0
Liege
Country [12] 0 0
Belgium
State/province [12] 0 0
Tienen
Country [13] 0 0
Denmark
State/province [13] 0 0
Ballerup
Country [14] 0 0
Germany
State/province [14] 0 0
Hessen
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Hong Kong
State/province [17] 0 0
Hong Kong
Country [18] 0 0
Hong Kong
State/province [18] 0 0
Shatin
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Suwon
Country [21] 0 0
Mexico
State/province [21] 0 0
Mexico, D.F.
Country [22] 0 0
Norway
State/province [22] 0 0
Bergen
Country [23] 0 0
Norway
State/province [23] 0 0
Hamar
Country [24] 0 0
Norway
State/province [24] 0 0
Oslo
Country [25] 0 0
Poland
State/province [25] 0 0
Grudziadz
Country [26] 0 0
Poland
State/province [26] 0 0
Warszawa
Country [27] 0 0
Poland
State/province [27] 0 0
Wroclaw
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Moscow
Country [29] 0 0
South Africa
State/province [29] 0 0
Panorama
Country [30] 0 0
South Africa
State/province [30] 0 0
Rosebank
Country [31] 0 0
South Africa
State/province [31] 0 0
Somerset West
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Santiago de Compostela

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.