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

NCT ID: NCT00471237

Last Updated: 2017-11-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 564 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-14
• Study Completion Date: 2008-12-26

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.

Conditions

Osteoporosis

Keywords

bone mineral density,; Ronacaleret; teriparatide; alendronate,; Post-menopausal women,; osteoporosis,; SB-751689

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

Bisphosphonate

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

Group Type: ACTIVE_COMPARATOR

Teriparatide

Intervention Type: DRUG

PTH (1-34)

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.

Group Type: EXPERIMENTAL

Ronacaleret

Intervention Type: DRUG

100mg, 200mg, 300mg, 400mg

Interventions

Ronacaleret

100mg, 200mg, 300mg, 400mg

Intervention Type: DRUG

Teriparatide

PTH (1-34)

Intervention Type: DRUG

Alendronate

Bisphosphonate

Intervention Type: DRUG

Other Intervention Names

SB-751689

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Oakland, California, United States

GSK Investigational Site

Palm Desert, California, United States

GSK Investigational Site

Walnut Creek, California, United States

GSK Investigational Site

Decatur, Georgia, United States

GSK Investigational Site

Bethesda, Maryland, United States

GSK Investigational Site

Akron, Ohio, United States

GSK Investigational Site

Cleveland, Ohio, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Duncansville, Pennsylvania, United States

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

St Leonards, New South Wales, Australia

GSK Investigational Site

Footscray, Victoria, Australia

GSK Investigational Site

Geelong, Victoria, Australia

GSK Investigational Site

Heidelberg, Victoria, Australia

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Liège, , Belgium

GSK Investigational Site

Tienen, , Belgium

GSK Investigational Site

Ballerup Municipality, , Denmark

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hong Kong, , Hong Kong

GSK Investigational Site

Shatin, , Hong Kong

GSK Investigational Site

Mexico City, , Mexico

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Hamar, , Norway

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Grudziądz, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Wroclaw, , Poland

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Panorama, , South Africa

GSK Investigational Site

Rosebank, , South Africa

GSK Investigational Site

Somerset West, , South Africa

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Suwon, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

Countries

United States; Argentina; Australia; Belgium; Denmark; Germany; Hong Kong; Mexico; Norway; Poland; Russia; South Africa; South Korea; Spain

References

Fitzpatrick LA, Dabrowski CE, Cicconetti G, Gordon DN, Fuerst T, Engelke K, Genant HK. Ronacaleret, a calcium-sensing receptor antagonist, increases trabecular but not cortical bone in postmenopausal women. J Bone Miner Res. 2012 Feb;27(2):255-62. doi: 10.1002/jbmr.554.

Reference Type: BACKGROUND

PMID: 22052452 (View on PubMed)

Fitzpatrick LA, Dabrowski CE, Cicconetti G, Gordon DN, Papapoulos S, Bone HG 3rd, Bilezikian JP. The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density. J Clin Endocrinol Metab. 2011 Aug;96(8):2441-9. doi: 10.1210/jc.2010-2855. Epub 2011 May 18.

Reference Type: DERIVED

PMID: 21593114 (View on PubMed)

Study Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Dataset Specification

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study Protocol

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

CR9108963

Identifier Type: -

Identifier Source: org_study_id