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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00548496




Registration number
NCT00548496
Ethics application status
Date submitted
23/10/2007
Date registered
24/10/2007
Date last updated
12/04/2017

Titles & IDs
Public title
A Phase IIa Study Of Men And Post-Menopausal Women With A Fractured Distal Radius
Scientific title
A Proof-of-Concept Study Of SB-751689 In Men And Post-menopausal Women With A Fractured Distal Radius
Secondary ID [1] 0 0
CR9108914
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fracture Healing 0 0
Condition category
Condition code
Injuries and Accidents 0 0 0 0
Fractures
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SB-751689
Other interventions - Placebo

Experimental: Placebo-Controlled based on the two Intervention Groups below - Placebo-Controlled based on the two Intervention Groups below.


Treatment: Drugs: SB-751689
SB-751689

Other interventions: Placebo
Placebo to match

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Data from the study will be used to determine if fracture healing time at 16 weeks is decreased in patients receiving SB-751689 and will determine future studies.
Timepoint [1] 0 0
16 Weeks
Secondary outcome [1] 0 0
Radiographic, functional, and quality of life assessments.
Timepoint [1] 0 0
16 Weeks

Eligibility
Key inclusion criteria
fracture/broken distal radius bone conservative treatment including closed reduction and
immobilization device men (>35 years <80) post-menopausal women (<80 yr)

Full In/Ex crit. and EPs as per Amendment 1, dated 7 Feb 08 Subject is willing and able to
provide written informed consent Unilateral, extra-articular distal radius fractures
AO/ASIF types 23-A2 and 23-A3 are permissible. (Arbeitsgemeinschaft für Osteosynthesefragen
[AO]/ Association for the Study of Internal Fixation [ASIF]). Multiple fractures of bones,
other than the limb with the distal radius fracture, are permissible if the subject can
perform the protocol-required procedures.

Received conservative treatment of the distal radius fracture, including closed reduction
and immobilization device (such as cast, splint, or brace) Ambulatory male and female
subjects aged =35 to <80 years of age who have sustained a closed, unilateral, fracture of
the distal radius no more than 5 days prior to randomization.

Females of non child-bearing potential defined as: >1 year postmenopausal, which can be >1
year of spontaneous amenorrhea or >1 year post surgical bilateral oophorectomy. Use
follicle stimulating hormone [FSH] levels >40mIU/mL to confirm surgical postmenopausal
status, where bilateral oophorectomy status is uncertain. Females of child-bearing
potential must have a negative urine bhCG pregnancy test at the Screening visit and agree
to practice acceptable highly effective methods of birth control throughout the duration of
the study. Highly effective birth control methods include those preventative measures taken
to avoid pregnancy that have a failure rate of less than 1% per year.

Subject who, in the opinion of the investigator, is willing and able to comply with the
requirements of the protocol, including ability to understand patient reported outcomes
(PRO) questionnaires
Minimum age
35 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-fracture occurred within 5 days of injury all AO B- and C-type prior fracture of the same
wrist placement of hardware (pins and plates) diseases affecting bone metabolism
inflammatory joint disease an increased risk of osteosarcoma malignant disease diagnosed
within the previous 5 years (except resected basal cell cancer) past or current history of
liver disease or known hepatic or biliary abnormalities treatment with fluoride (dose
greater than 10 mg/day) within the previous 5 years for osteoporosis limitations of prior
treatment with an oral bisphosphonate

Any treatment of a fractured distal radius that occurred more than 5 days after the
fracture sustaining injury All B- and C-type fractures (intra-articular) according to AO
Fracture classification or any distal radius fracture that would likely require open
reduction and internal fixation. All additional fractures in the limb (including hand and
humerus) with the distal radial fracture are excluded. Any fracture of the contralateral
upper or lower arm, wrist or hand that would interfere with obtaining measurements on the
dynamometer are excluded. Pathological (tumor-related) fractures Prior fracture of the same
wrist as an adult Hardware including pins or plates in the wrist (either prior or current
injury) History of or concurrent synovial pseudoarthrosis, congenital pseudoarthrosis, or
active osteomyelitis History or concurrent diseases affecting bone metabolism (e.g.,
osteomalacia, hyperparathyroidism, etc.) History of skeletal immaturity Active disease or
history of inflammatory joint disease (e.g., rheumatoid arthritis, lupus, psoriatic
arthritis) that would interfere with imaging of the fracture Subjects receiving thyroid
hormone replacement therapy should have thyroid stimulating hormone (TSH) levels
measured.Subjects will be excluded if TSH levels are <0.1 or >10.0 mIU/L. However, subjects
will not be excluded if TSH is in the range 0.1-4.5 mIU/L. If TSH is >4.5 to £10.0 mIU/L,
measure T4 and exclude the subject only if the T4 is outside the normal range History of or
active nephrolithiasis (kidney stones) Subjects at increased risk of osteosarcoma such as
those with Paget's disease of bone or history of any prior external beam or implant
radiation therapy involving the skeleton Malignant disease diagnosed within the previous 5
years (except resected basal cell cancer) Active or history of malabsorption (e.g., history
of celiac disease, irritable bowel syndrome, or inflammatory bowel disease) Note: Subjects
are not excluded because of previous or active gastrointestinal disease (i.e., prior
history of non-recurrent peptic ulcer disease). Symptoms of dyspepsia, or Gastroesophageal
Reflux Disease (GERD) must be able to be controlled by occasional use (not more than 3
doses per week) of a histamine-2 receptor antagonist Past or current history of liver
disease or known hepatic or biliary abnormalities (with the exception of previously
documented diagnosis of Gilbert's syndrome) Drug or alcohol abuse (past or current) within
the previous 12 months A history of risk factors for Torsades de Pointes (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome) A marked baseline prolongation of
corrected QT interval (e.g., QTc interval ³450 msec on the Screening ECG corrected by
either Bazett's or Fridericia's methodology) Surgical and medical conditions: Presence of
the following conditions within 6 months prior to screening: myocardial infarction,
coronary bypass surgery, coronary artery angioplasty, unstable angina, clinically evident
congestive heart failure, cardiac pacemaker, or cerebrovascular accident: have currently
known, suspected, or history of neurological diseases that affect the clinical assessments
of healing; Cardiac arrhythmia: significant cardiac arrhythmias shown on screening ECG (as
confirmed by eRT report), or a known or suspected history of significant cardiac
arrhythmia's within 6 months prior to screening. i.e., pre-excitation syndromes, sinus
pause >3 seconds, non-sustained ventricular tachycardia (³3 consecutive ectopic beats),
sustained ventricular tachycardia (³30 consecutive ectopic beats), sustained
supraventricular tachycardia (³30 consecutive ectopic beats), accessory pathway
tachycardia, bradycardia (heart rate <50 beats per minute), atrial flutter, atrial
fibrillation, ectopic pacemaker, sick sinus syndrome, atrioventricular block (second or
third degree), or bundle branch block.

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
[e.g., human immunodeficiency virus infection and significant mental illness] Inability to
swallow whole tablets Any previous treatment with strontium ranelate or intravenous
bisphosphonate Any previous treatment with an oral bisphosphonate as follows: any treatment
within the last 6 months; = 1 month cumulative treatment within the last 12 months; = 3
months cumulative treatment within the past 2 years, or = 2 years cumulative treatment
within the past 5 years Treatment with fluoride (dose greater than 10mg/day) within the
previous 5 years for osteoporosis Treatment with PTH, PTH analogues or similar anabolic
agent for osteoporosis within the last 2 years Treatment with other drugs affecting bone
metabolism within the last 6 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, selective estrogen receptor modulators
[SERMs] such as raloxifene, anabolic steroids/androgens such as dehydroepiandrosterone
[DHEA] or its sulfated form [DHEAS], nandrolone, tibolone, active vitamin D
analogs/metabolites that are prescribed for the treatment of osteoporosis or other
conditions such as 1,25-dihydroxy vitamin D [calcitriol] or 1-alpha-hydroxyvitamin D3
[1-alpha hydroxycholecalciferol], calcitonin); Calcineurin inhibitors (e.g., cyclosporine,
tacrolimus) or methotrexate Contraindications to therapy with calcium or vitamin D Any
subject who received treatment with the macrolide antibiotics: clarithromycin,
erythromycin, telithromycin, and troleandomycin within 2 days prior to the Baseline visit
Administration of any investigational drug within 90 days preceding the first dose of the
study medication Current treatment with potent P-glycoprotein and/or potent CYP3A
inhibitors is prohibited: Diltiazem and verapamil; any oral azole antifungal (e.g.,
ketoconazole, itraconazole, fluconazole); Cyclosporine or oral tacrolimus; Ritonavir;
Quinidine; Nefazodone Concomitant therapy with proton pump inhibitors (e.g., esomeprazole,
lansoprazole, omeprazole, pantoprazole, and rabeprazole) is prohibited. Daily, chronic use
(>3 doses per week) of histamine-2 receptor antagonists (e.g., cimetidine, famotidine,
nizatidine, and ranitidine) is prohibited. Antacids should not be administered within 2
hours (before or after) administration of study medication.

Vitamin A in excess of 10,000 IU per day, heparin, lithium, or anticonvulsant medications
(except benzodiazepines) Current therapy with digoxin Subjects taking daily, long-term
(i.e., > 1 year) non-steroidal anti-inflammatory drugs (NSAIDs) for diseases such as
inflammatory arthritis are excluded. The use of low dose aspirin for prevention of heart
disease is permitted. Short term use of NSAIDs is permitted for acute pain management but
the use of alternative, non-NSAIDs is encouraged Total serum calcium levels outside the
local laboratory reference range at the Screening visit Liver chemistries (aspartate
aminotransferase [AST], alanine aminotransferase [ALT], or total bilirubin) exceeding
2-fold the upper limit of the local laboratory reference range at the Screening visit
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) Women who are pregnant or breast-feeding are not allowed in the study. Females of
child-bearing potential must have a negative urine bhCG pregnancy test at the Screening and
Randomization visit and agree to practice acceptable highly effective methods of birth
control through the duration of the study and for 4 weeks following the last dose of study
medication. Highly effective birth control methods include those preventative measures
taken to avoid pregnancy that have a failure rate of less than 1% per year.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
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 - Kogarah
Recruitment hospital [2] 0 0
GSK Investigational Site - St Leonards
Recruitment hospital [3] 0 0
GSK Investigational Site - Geelong
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Córdova
Country [3] 0 0
Argentina
State/province [3] 0 0
Ciudad Autónoma de Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Quilmes
Country [5] 0 0
Argentina
State/province [5] 0 0
Rosario
Country [6] 0 0
Argentina
State/province [6] 0 0
San Juan
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Praha 2
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Praha 4
Country [9] 0 0
Hong Kong
State/province [9] 0 0
Hong Kong
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Netherlands
State/province [11] 0 0
Almelo
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Netherlands
State/province [13] 0 0
Leiden
Country [14] 0 0
Romania
State/province [14] 0 0
Bucharest
Country [15] 0 0
Romania
State/province [15] 0 0
Cluj-Napoca
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Ekaterinburg
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Yaroslavl
Country [19] 0 0
South Africa
State/province [19] 0 0
Bryanston
Country [20] 0 0
South Africa
State/province [20] 0 0
Pinelands
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Santiago de Compostela
Country [23] 0 0
Spain
State/province [23] 0 0
Sevilla
Country [24] 0 0
Sweden
State/province [24] 0 0
Göteborg
Country [25] 0 0
Sweden
State/province [25] 0 0
Kungälv
Country [26] 0 0
Sweden
State/province [26] 0 0
Mölndal
Country [27] 0 0
Taiwan
State/province [27] 0 0
Changhua
Country [28] 0 0
Taiwan
State/province [28] 0 0
Taichung
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Flintshire
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Midlothian

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a study designed to test the safety and effectiveness of SB-751689 in the treatment
of a distal radius fracture in post-menopausal women and men in comparison to placebo to
determine if healing time of the fracture can be decreased.
Trial website
https://clinicaltrials.gov/show/NCT00548496
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00548496