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

This study has been terminated.
(Terminated for futility by sponsor after a pre-planned interim review of data)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00471237
First received: May 7, 2007
Last updated: April 19, 2012
Last verified: March 2011
  Purpose

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 Intervention Phase
Postmenopausal Osteoporosis
Osteoporosis
Drug: Ronacaleret
Drug: Teriparatide
Drug: Alendronate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Data from this study, along with other data, will be used to select a dose of SB-751689 for further evaluation based on the effect seen on bone mineral density, safety and tolerability, in comparison with placebo and 2 active comparators. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bone mineral density of the lumbar spine and hip, volumetric bone mineral density at the hip and spine, biomarkers of bone turnover [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

Enrollment: 569
Study Start Date: May 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: SB-751689

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00471237

  Show 45 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00471237     History of Changes
Other Study ID Numbers: CR9108963
Study First Received: May 7, 2007
Last Updated: April 19, 2012
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
Argentina: Ministry of Health - A.N.M.A.T
Belgium: Agence Fédérale des Médicaments et des Produits de la Santé
Norway: Statens Legemiddelverk
Russia: Russian Ministry of Health
Denmark: Lægemiddelstyrelsen
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
South Africa: Medicines Control Council
Poland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBK
Mexico: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
South Korea: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
bone mineral density,
Ronacaleret
teriparatide
alendronate,
Post-menopausal women,
osteoporosis,
SB-751689

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Alendronate
Teriparatide
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014