Fractures, BonePhase 3NCT01920568
A Study to Compare Denosumab With Zoledronic Acid in Subjects With Bone Metastases From Solid Tumors
A Phase 3 study testing Denosumab 70 mg/mL, Zoledronic acid 4 mg and Calcium supplement in people with Fractures, Bone, run by GlaxoSmithKline at 25 sites in 3 countries.
Trial summary
This is a randomized, double-blind, double-dummy study designed to provide bridging data in an Asian population to Amgen's studies of denosumab in subjects with bone metastases from solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fractures, Bone
- What is being tested?
- Denosumab 70 mg/mL, Zoledronic acid 4 mg and Calcium supplement
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 487 participants
- Where
- 25 sitesin 3 countries
- Study dates
- Aug 2013to Apr 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject understands the nature and purpose of this study and the study procedures, which have been explained by the Investigator or delegate, and subject has signed the written informed consent for the overall study. The subject must sign a separate written informed consent to be eligible for enrolment in the pharmacokinetic substudy.
- Adult (aged >=18 years) of Asian ancestry with a histologically or cytologically confirmed solid tumor. In addition, subjects who are enrolled at a center in mainland China or at an SFDA-certified center in Hong Kong including the approximately 33 subjects in the pharmacokinetic substudy must be of Chinese race, ancestry, or heritage. Subjects enrolled in other regions or countries, such as Taiwan and Singapore, or at a non-SFDA-certified center in Hong Kong, are not required to be of Chinese race or ancestry.
- Current or prior documented radiographic evidence (i.e., x-ray, computer tomography [CT], or magnetic resonance imaging [MRI]) of at least 1 bone metastasis.
- Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined below, during the study and for 6 months after end of study treatment. Women who report having a pregnancy during this study will be followed for birth outcomes. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: An intrauterine device or intrauterine system with a documented failure rate of less than 1% per year; Male partner sterilization prior to the female subject's enrollment and the male is the sole sexual partner for that subject; the information on the male sterility can come from the site personnel's review of subject's medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history; complete abstinence from sexual intercourse for 14 days prior to first dose of study treatment, through the dosing period, and for at least 7 months after the last dose of study treatment; double-barrier contraception: male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository); implants of levonorgestrel or etonogestrel where not contraindicated for this patient population or per local practice; injectable progesterone where not contraindicated for this patient population or per local practice; percutaneous contraceptive patches where not contraindicated for this patient population or per local practice; Oral contraceptives (either combined or progesterone only) where not contraindicated for this patient population or per local practice. Females of child bearing potential who do not have male partners as part of their preferred and usual lifestyle are not required to use contraception.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (refer protocol for details).
- Adequate baseline organ function as defined by the following criteria: Serum aspartate aminotransferase (AST) <=2.0 x upper limit of normal (ULN); Serum alanine aminotransferase (ALT) <=2.0 x ULN; Serum total bilirubin <=1.0 x ULN; creatinine clearance (calculated using the Cockcroft-Gault formula) >=30 milliliter per minute (mL/min); serum calcium or albumin-adjusted serum calcium >=2.0 millimole per liter (mmol/L) (8.0 mg/dL) and <=2.9 mmol/L (11.5 miligram per deciliter [mg/dL]). Subjects must not have taken supplemental calcium for at least 8 hours prior to collection of the blood sample for screening serum calcium determination.
- Life expectancy of at least 6 months, in the opinion of the Investigator.
Who cannot join
- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that, in the opinion of the Investigator, could interfere with subject's safety, obtaining informed consent or compliance to the study procedures; The Investigator should consult the GSK Medical Monitor prior to enrolling a subject if s/he is unsure if a condition might interfere with the subject's safety or participation in this study.
- Any prior treatment with intravenous (IV) or oral bisphosphonates.
- Prior treatment with denosumab.
- Planned radiation therapy or surgery to bone.
- Known brain metastases.
- Prior history or current evidence of osteomyelitis or osteonecrosis of the jaws (ONJ), an active dental or jaw condition that requires oral surgery, non-healed dental or oral surgery, or planned invasive dental procedure over the course of the study.
Show all 11Show fewer
- Evidence of any of the following conditions per subject self report or medical chart review: any prior or current malignancy (other than the cancer under study in this protocol) with active disease within 3 years before randomization; unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); known infection with human immunodeficiency virus (HIV); active infection with hepatitis B or hepatitis C virus.
- Pregnant women, women planning to become pregnant within 7 months after end of study treatment, and women who are breastfeeding. Women who are breast feeding should discontinue nursing prior to the first dose of study treatment and should refrain from nursing throughout the treatment period and for 7 months following their last dose of study treatment.
- Male subjects unable or unwilling to use adequate contraception methods during the study and for 6 months after end of study treatment should be excluded.
- Subject is currently enrolled in another investigational device or investigational product study, or has not completed at least 30 days, 5 half lives, or the duration of biological effect, whichever is longer, since ending such a study.
- Known sensitivity to any of the investigational products or supplements to be administered during the study (i.e., zoledronic acid, mammalian derived products, calcium, or vitamin D).
Trial locations and contacts
25 sites in 3 countries.
25 sites in 3 countries
China22 sites
GSK Investigational Site
Beijing, 100021
GSK Investigational Site
Beijing, 100034
GSK Investigational Site
Beijing, 100036
GSK Investigational Site
Beijing, 100071
GSK Investigational Site
Changchun, Jilin, 130012
GSK Investigational Site
Chengdu, Sichuan, 610041
GSK Investigational Site
Fuzhou, 350001
GSK Investigational Site
Guangzhou, Guangdong, 510060
GSK Investigational Site
Guangzhou, Guangdong, 510120
GSK Investigational Site
Guangzhou, Guangdong, 510515
GSK Investigational Site
Hangzhou, Zhejiang, 310003
GSK Investigational Site
Hangzhou, 310016
GSK Investigational Site
Harbin
GSK Investigational Site
Nanjing, Jiangsu, 210002
GSK Investigational Site
Nanjing, Jiangsu, 210009
GSK Investigational Site
Shanghai, 200025
GSK Investigational Site
Shanghai, 200032
GSK Investigational Site
Shanghai, 200070
GSK Investigational Site
Shanghai, 200080
GSK Investigational Site
Shanghai, 200233
GSK Investigational Site
Tianjin, 300060
GSK Investigational Site
Wuhan, Hubei, 430030
Taiwan2 sites
GSK Investigational Site
Taichung, 404
GSK Investigational Site
Taoyuan, 333
About this study
Official title: DCA114273: A Study Comparing Denosumab With Zoledronic Acid in Subjects of Asian Ancestry With Bone Metastases From Solid Tumors
This is a randomized, double-blind, double-dummy study designed to provide bridging data in an Asian population to Amgen's studies of denosumab in subjects with bone metastases from solid tumors. The study is designed to provide data to a large global dataset of phase-III studies including breast cancer, prostate cancer, and all solid tumors, plus multiple myeloma, to support the regulatory approval for marketing and patient access to denosumab for the prevention of SREs in Chinese subjects with bone metastases from solid tumors. The primary objective of this study is to evaluate and compare the percent change from baseline to Week 13 in the bone marker urinary amino-terminal cross-linking telopeptide of type I collagen (uNTx) corrected for urine creatinine (uNTx/uCr) in subjects treated with denosumab to those treated with zoledronic acid. The study is designed to test the superiority of denosumab over zoledronic acid.
- Conditions
- Fractures, Bone
- Being tested
- Denosumab 70 mg/mL, Zoledronic acid 4 mg, Placebo IV, Placebo SC, Calcium supplement
- Keywords
- GSK2371746, Denosumab, China, skeletal-related events, bone metastases, bridging study, solid tumors
- Medical subject headings
- Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Denosumab 70 mg/mLBiological
Denosumab will be given as a SC injection of 120 mg by administering a 1.7 mL volume in a single injection
Zoledronic acid 4 mgDrug
Zoledronic acid 4 mg (or equivalent clearance-adjusted dose in subjects with baseline creatinine clearance <=60 ml/min) will be diluted in either 0.9% sodium chloride or 5% dextrose injection and administered IV.
Placebo IVDrug
The placebo will consist of 1.7 mL 0.9% w/v sodium chloride
Placebo SCDrug
The placebo will consist of either 0.9% w/v sodium chloride or 5% dextrose injection
Calcium supplementDietary supplement
Subjects are strongly recommended to take daily supplements of at least 500 mg calcium from the day of consent and until completion of the Week 73 follow-up visit.
Vitamin D supplementDietary supplement
Subjects are strongly recommended to take daily supplements of at least 400 IU of vitamin D from the day of consent and until completion of the Week 73 follow-up visit.
| Study group | Role | What they receive |
|---|---|---|
| Denosumab 120 mg | Experimental | Subjects will be administered with Denosumab 120 mg subcutaneous (SC) injection for a maximum of 13 doses and placebo IV infusion over \>=15 minutes once every 4 weeks. Receives: Biological: Denosumab 70 mg/mL; Drug: Placebo IV; Dietary Supplement: Calcium supplement; Dietary Supplement: Vitamin D supplement |
| Zoledronic acid 4 mg | Experimental | Subjects will be administered with Zoledronic acid 4 mg IV infusion over a minimum of 15 minutes for a maximum of 13 doses and placebo SC once every 4 weeks. Receives: Drug: Zoledronic acid 4 mg; Drug: Placebo SC; Dietary Supplement: Calcium supplement; Dietary Supplement: Vitamin D supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change (Chg) From Baseline (BL) to Week (Wk)13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr)
uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment (trt). uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Primary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Asian ancestry with bone metastases from solid tumors. BL value is the most recent, non-missing value prior to or on the 1st study trt dose date. Chg from BL is the value at Wk13 minus BL value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.
Measured: Baseline (BL) and Week (Wk) 13
Secondary outcomes (8)
Percentage Change From Baseline to Week 13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) in Chinese Participants.
uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment. uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Secondary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Chinese ancestry with bone metastases from solid tumors. Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Week 13 minus Baseline value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.
Measured: Baseline and Week 13
Percentage Change From Baseline to Week 13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) in Participants With Advanced Breast Cancer.
uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment. uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Secondary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in breast cancer par. with bone metastases from solid tumors. Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Week 13 minus Baseline value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.
Measured: Baseline and Week 13
Percent Change From Baseline in the Serum Bone-specific Alkaline Phosphatase (s-BALP) at Week 13.
Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Indicated visit minus Baseline value. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100.
Measured: Baseline and Week 13
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, non-fatal SAEs, fatal SAEs have been presented.
Measured: From start of IP through the Study Phase (49 weeks post-dose) (assessed up to 73 weeks)
Number of Participants With Worst-case (WC) On-therapy Increase in the Indicated Clinical Chemistry Parameters From Baseline Grade to the Indicated Grade.
Clinical chemistry parameters were measured at the Screening and Weeks 2, 5, 9, 13, 25, 37, and 53 visits. Clinical chemistry parameters measured on-study included albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, calcium (Ca), creatinine, magnesium, and phosphorous (P) inorganic. All reported values are of participants with worst-case on-therapy increase to the specified grade: Any increase, that is, worst-case increase to grade 1, 2, 3, or 4 (any grade); worst-case increase to grade 3 (WC G3); and worst-case increase to grade 4 (WC G4). The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) was used for grading. Participants with missing Baseline grade were assumed to have a Baseline grade of 0. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Measured: Baseline and up to last study-related visit (up to 53 weeks)
Number of Participants With Worst-case On-therapy Increase in the Indicated Hematology Parameters From Baseline Grade to the Indicated Grade.
Hematology parameters included hemoglobin, lymphocytes, platelet count, total neutrophils, white blood cell (WBC) count. All reported values are of participants with worst-case on-therapy increase to the specified grade: Any increase, that is, worst-case increase to grade 1, 2, 3, or 4 (any grade); worst-case increase to grade 3 (WC G3); and worst-case increase to grade 4 (WC G4). Participants with missing Baseline grade were assumed to have a Baseline grade of 0. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Measured: Baseline and up to last study-related visit (up to 53 weeks)
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Day 1, Week 25 and Week 53.
Anti-denosumab antibody formation was assessed at Day 1, Week 25 and Week 53. Binding antibody assay was used to assess number of participants with anti-denosumab antibody.
Measured: Day 1, Week 25 and Week 53
Serum Concentration of Denosumab on Day 1, at Week 2, Week 5, Week 9, Week 13, Week 17, Week 19, Week 21, Week 25 and Week 49
Blood samples were drawn on study Day 1, pre-dose; 4 hours, 24 hours, and at Week 2 (168 hours); then pre-dose at Week 5, Week 9, Week 13, Week 17, Week 19 (no dose), Week 21, Week 25, and Week 49.
Measured: Samples were collected at pre-dose (Day 1); 4 hours, 24 hours, 168 hours post-dose; pre-dose at Week 5, Week 9, Week 13, Week 17; Week 19 (at 336 hours); pre-dose at Week 21, Week 25, Week 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2013 (estimated)
- Study startAug 2013
- Primary completionFeb 2015
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Fractures, BoneStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 487 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01920568
- Sponsor's protocol ID
- 114273
- Status last verified
- Jul 2016
- First submitted
- 8 Aug 2013
- Last updated
- 16 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DCA114273: A Study Comparing Denosumab With Zoledronic Acid in Subjects of Asian Ancestry With Bone Metastases From Solid Tumors
- ClinicalTrials.gov ID
- NCT01920568
- Acronym / sponsor ID
- 114273
- Conditions
- Fractures, Bone
- Keywords
- GSK2371746, Denosumab, China, skeletal-related events, bone metastases, bridging study, solid tumors
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 487 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Amgen
- Study start
- Aug 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 12 Aug 2013 (estimated)
- Results
- Posted 25 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, double-dummy study designed to provide bridging data in an Asian population to Amgen's studies of denosumab in subjects with bone metastases from solid tumors. The study is designed to provide data to a large global dataset of phase-III studies including breast cancer, prostate cancer, and all solid tumors, plus multiple myeloma, to support the regulatory approval for marketing and patient access to denosumab for the prevention of SREs in Chinese subjects with bone metastases from solid tumors. The primary objective of this study is to evaluate and compare the percent change from baseline to Week 13 in the bone marker urinary amino-terminal cross-linking telopeptide of type I collagen (uNTx) corrected for urine creatinine (uNTx/uCr) in subjects treated with denosumab to those treated with zoledronic acid. The study is designed to test the superiority of denosumab over zoledronic acid.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab 120 mg | Experimental | Biological: Denosumab 70 mg/mL, Drug: Placebo IV, Dietary Supplement: Calcium supplement, Dietary Supplement: Vitamin D supplementSubjects will be administered with Denosumab 120 mg subcutaneous (SC) injection for a maximum of 13 doses and placebo IV infusion over \>=15 minutes once every 4 weeks. |
| Zoledronic acid 4 mg | Experimental | Drug: Zoledronic acid 4 mg, Drug: Placebo SC, Dietary Supplement: Calcium supplement, Dietary Supplement: Vitamin D supplementSubjects will be administered with Zoledronic acid 4 mg IV infusion over a minimum of 15 minutes for a maximum of 13 doses and placebo SC once every 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subject understands the nature and purpose of this study and the study procedures, which have been explained by the Investigator or delegate, and subject has signed the written informed consent for the overall study. The subject must sign a separate written informed consent to be eligible for enrolment in the pharmacokinetic substudy.
- Adult (aged >=18 years) of Asian ancestry with a histologically or cytologically confirmed solid tumor. In addition, subjects who are enrolled at a center in mainland China or at an SFDA-certified center in Hong Kong including the approximately 33 subjects in the pharmacokinetic substudy must be of Chinese race, ancestry, or heritage. Subjects enrolled in other regions or countries, such as Taiwan and Singapore, or at a non-SFDA-certified center in Hong Kong, are not required to be of Chinese race or ancestry.
- Current or prior documented radiographic evidence (i.e., x-ray, computer tomography [CT], or magnetic resonance imaging [MRI]) of at least 1 bone metastasis.
- Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined below, during the study and for 6 months after end of study treatment. Women who report having a pregnancy during this study will be followed for birth outcomes. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: An intrauterine device or intrauterine system with a documented failure rate of less than 1% per year; Male partner sterilization prior to the female subject's enrollment and the male is the sole sexual partner for that subject; the information on the male sterility can come from the site personnel's review of subject's medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history; complete abstinence from sexual intercourse for 14 days prior to first dose of study treatment, through the dosing period, and for at least 7 months after the last dose of study treatment; double-barrier contraception: male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository); implants of levonorgestrel or etonogestrel where not contraindicated for this patient population or per local practice; injectable progesterone where not contraindicated for this patient population or per local practice; percutaneous contraceptive patches where not contraindicated for this patient population or per local practice; Oral contraceptives (either combined or progesterone only) where not contraindicated for this patient population or per local practice. Females of child bearing potential who do not have male partners as part of their preferred and usual lifestyle are not required to use contraception.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (refer protocol for details).
Key exclusion criteria (11 listed)
- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that, in the opinion of the Investigator, could interfere with subject's safety, obtaining informed consent or compliance to the study procedures; The Investigator should consult the GSK Medical Monitor prior to enrolling a subject if s/he is unsure if a condition might interfere with the subject's safety or participation in this study.
- Any prior treatment with intravenous (IV) or oral bisphosphonates.
- Prior treatment with denosumab.
- Planned radiation therapy or surgery to bone.
- Known brain metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Denosumab 70 mg/mLDenosumab will be given as a SC injection of 120 mg by administering a 1.7 mL volume in a single injection | Biological | Denosumab 120 mg |
| Zoledronic acid 4 mgZoledronic acid 4 mg (or equivalent clearance-adjusted dose in subjects with baseline creatinine clearance <=60 ml/min) will be diluted in either 0.9% sodium chloride or 5% dextrose injection and administered IV. | Drug | Zoledronic acid 4 mg |
| Placebo IVThe placebo will consist of 1.7 mL 0.9% w/v sodium chloride | Drug | Denosumab 120 mg |
| Placebo SCThe placebo will consist of either 0.9% w/v sodium chloride or 5% dextrose injection | Drug | Zoledronic acid 4 mg |
| Calcium supplementSubjects are strongly recommended to take daily supplements of at least 500 mg calcium from the day of consent and until completion of the Week 73 follow-up visit. | Dietary supplement | Denosumab 120 mg, Zoledronic acid 4 mg |
| Vitamin D supplementSubjects are strongly recommended to take daily supplements of at least 400 IU of vitamin D from the day of consent and until completion of the Week 73 follow-up visit. | Dietary supplement | Denosumab 120 mg, Zoledronic acid 4 mg |
Primary outcome
Percent Change (Chg) From Baseline (BL) to Week (Wk)13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr)
Time frame: Baseline (BL) and Week (Wk) 13
uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment (trt). uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Primary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Asian ancestry with bone metastases from solid tumors. BL value is the most recent, non-missing value prior to or on the 1st study trt dose date. Chg from BL is the value at Wk13 minus BL value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value.
8 secondary outcomes
Percentage Change From Baseline to Week 13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) in Chinese Participants.
Time frame: Baseline and Week 13
Percentage Change From Baseline to Week 13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) in Participants With Advanced Breast Cancer.
Time frame: Baseline and Week 13
Percent Change From Baseline in the Serum Bone-specific Alkaline Phosphatase (s-BALP) at Week 13.
Time frame: Baseline and Week 13
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
Time frame: From start of IP through the Study Phase (49 weeks post-dose) (assessed up to 73 weeks)
Number of Participants With Worst-case (WC) On-therapy Increase in the Indicated Clinical Chemistry Parameters From Baseline Grade to the Indicated Grade.
Time frame: Baseline and up to last study-related visit (up to 53 weeks)
Number of Participants With Worst-case On-therapy Increase in the Indicated Hematology Parameters From Baseline Grade to the Indicated Grade.
Time frame: Baseline and up to last study-related visit (up to 53 weeks)
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Day 1, Week 25 and Week 53.
Time frame: Day 1, Week 25 and Week 53
Serum Concentration of Denosumab on Day 1, at Week 2, Week 5, Week 9, Week 13, Week 17, Week 19, Week 21, Week 25 and Week 49
Time frame: Samples were collected at pre-dose (Day 1); 4 hours, 24 hours, 168 hours post-dose; pre-dose at Week 5, Week 9, Week 13, Week 17; Week 19 (at 336 hours); pre-dose at Week 21, Week 25, Week 49
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
25 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Denosumab 70 mg/mL, Zoledronic acid 4 mg and Calcium supplement in people with Fractures, Bone, run by GlaxoSmithKline at 25 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in China, Taiwan, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change (Chg) From Baseline (BL) to Week (Wk)13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) (time frame: Baseline (BL) and Week (Wk) 13). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2017.