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

NCT00471237 | Terminated Phase 2 Results DMC

• 1 other identifier: CR9108963
• Study Type: interventional
• Target: 564
• Locations: 14 countries
• Sites: 49

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

Outcome Measures

Primary Outcomes (8)

• 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)

  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.

  Baseline (Day 0) and 12 Months

• Number of Participants With Hypercalcemia

  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.

  Up to Month 12

• Number of Participants Withdrew Due to Hypercalcemia

  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.

  Up to Month 12

• Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit

  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.

  Up to Month 12

• Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit

  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.

  Up to 12 Months

• Number of Participant With Electrocardiogram (ECG) Findings Reported as Adverse Event

  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.

  Up to 12 months

• Mean Change From Baseline in Height

  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.

  Baseline (Day 0), Month 6, 12 and early withdrawal

• Mean Change From Baseline in Weight

  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.

  Baseline (Day 0), Month 6, 12 and early withdrawal

Secondary Outcomes (14)

• 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

• 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

• Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)

  Baseline (Day 0), Month 5, 6 and 12

• Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip and Lumbar Spine as Measured by Quantitative Computer Tomography (QCT) Scans

  Baseline (Day 0) and Month 12

• Percent Change From Baseline to Month 12 in the Total Vertebra Integral VOI at the Lumbar Spine as Measured by QCT Scans

  Baseline (Day 0) and Month 12

Study Arms (4)

Placebo

NO INTERVENTION

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

Alendronate

ACTIVE COMPARATOR

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

Teriparatide

ACTIVE COMPARATOR

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

Ronacaleret

EXPERIMENTAL

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

Interventions

Ronacaleret DRUG

100mg, 200mg, 300mg, 400mg

Also known as: SB-751689

Ronacaleret

Teriparatide DRUG

PTH (1-34)

Teriparatide

Alendronate DRUG

Bisphosphonate

Alendronate

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (49)

GSK Investigational Site

Oakland, California, 94609, United States

Location

GSK Investigational Site

Palm Desert, California, 92260, United States

Location

GSK Investigational Site

Walnut Creek, California, 94598, United States

Location

GSK Investigational Site

Decatur, Georgia, 30033, United States

Location

GSK Investigational Site

Bethesda, Maryland, 20817, United States

Location

GSK Investigational Site

Akron, Ohio, 44313, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44195, United States

Location

GSK Investigational Site

Portland, Oregon, 97213, United States

Location

GSK Investigational Site

Duncansville, Pennsylvania, 16635, United States

Location

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1117ABH, Argentina

Location

GSK Investigational Site

Buenos Aires, 1012, Argentina

Location

GSK Investigational Site

Buenos Aires, C1128AAF, Argentina

Location

GSK Investigational Site

St Leonards, New South Wales, 2065, Australia

Location

GSK Investigational Site

Footscray, Victoria, 3011, Australia

Location

GSK Investigational Site

Geelong, Victoria, 3220, Australia

Location

GSK Investigational Site

Heidelberg, Victoria, 3081, Australia

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Liège, 4020, Belgium

Location

GSK Investigational Site

Tienen, 3300, Belgium

Location

GSK Investigational Site

Ballerup Municipality, 2750, Denmark

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60528, Germany

Location

GSK Investigational Site

Berlin, 10559, Germany

Location

GSK Investigational Site

Berlin, 12203, Germany

Location

GSK Investigational Site

Berlin, 12247, Germany

Location

GSK Investigational Site

Berlin, 13125, Germany

Location

GSK Investigational Site

Hamburg, 22143, Germany

Location

GSK Investigational Site

Hamburg, 22415, Germany

Location

GSK Investigational Site

Hong Kong, Hong Kong

Location

GSK Investigational Site

Shatin, Hong Kong

Location

GSK Investigational Site

Mexico City, 14050, Mexico

Location

GSK Investigational Site

Bergen, 5094, Norway

Location

GSK Investigational Site

Hamar, 2317, Norway

Location

GSK Investigational Site

Oslo, 0176, Norway

Location

GSK Investigational Site

Grudziądz, 86-300, Poland

Location

GSK Investigational Site

Warsaw, 02-341, Poland

Location

GSK Investigational Site

Wroclaw, 50-088, Poland

Location

GSK Investigational Site

Moscow, 117292, Russia

Location

GSK Investigational Site

Moscow, 127299, Russia

Location

GSK Investigational Site

Panorama, 7500, South Africa

Location

GSK Investigational Site

Rosebank, 2196, South Africa

Location

GSK Investigational Site

Somerset West, 7130, South Africa

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Suwon, 443-721, South Korea

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Barcelona, 08022, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15705, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

Related Publications (2)

• 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.

  PMID: 22052452 BACKGROUND

• 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.

  PMID: 21593114 DERIVED

Related Links

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

MeSH Terms

Conditions

Osteoporosis

Interventions

ronacaleret; Teriparatide; Alendronate

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Limitations and 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.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2007
• First Posted: May 9, 2007
• Study Start: May 14, 2007
• Primary Completion: December 26, 2008
• Study Completion: December 26, 2008
• Last Updated: November 7, 2017
• Results First Posted: September 5, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

NO (3); PL (3); AU (4); RU (2); ZA (3); KR (2); ES (6); US (9); BE (3); AR (3); HK (2); DK (1); DE (7); ME (1)