Transplantation, Stem CellPhase 1NCT01802892
Study in Healthy Volunteers, to Evaluate the Safety, Efficacy and Dose Responses of SB-751689 (Ronacaleret)
A Phase 1 study testing Ronacaleret 100 mg, Ronacaleret 400 mg and Plerixafor in people with Transplantation, Stem Cell, run by GlaxoSmithKline at 1 site in United States.
Trial summary
The present study aims to evaluate the impact of 5 days oral administration of ronacaleret 100 miligram (mg) and 400 mg on changes in circulating CD34+ cells, when ronacaleret is followed by the administration of a single dose of plerixafor in healthy human volunteers. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Transplantation, Stem Cell
- What is being tested?
- Ronacaleret 100 mg, Ronacaleret 400 mg and Plerixafor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2012to 2 Apr 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- A male or female between 18 and 65 years of age (inclusive).
- Healthy as determined by a physician, based on a medical evaluation and with an estimated Glomerular Filtration Rate (GFR) of >=60 mL/min /1.73 m^2 using the four variable Modification of Diet in Renal Disease (MDRD) equation.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Female of non-child bearing potential, or female subjects and male subjects with female partners of child-bearing potential willing to use protocol-specified methods of contraception to prevent pregnancy during the study.
- Body weight of 55 kg or more and body mass index (BMI) of 20.0 to 35.0 kg/m^2 (inclusive).
- Capable of giving written informed consent.
Who cannot join
- A positive pre-study drug/alcohol screen.
- A positive test for HIV, B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- History of or therapy for osteoporosis
- Subject has had treatment for any condition relating to the thyroid/parathyroid gland which in the opinion of the investigator may influence the subjects production of PTH
- Subjects with any contraindications or know allergies to receiving plerixafor
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones).
Show all 15Show fewer
- Subjects taking calcium and/or vitamin D supplements, during or within 2 weeks of study initiation
- Subjects taking any concomitant medications
- Specific laboratory abnormalities at screening like Serum calcium (total or albumin-adjusted) outside the central laboratory reference range, PTH outside the normal range, Creatine phosphokinase (CPK) outside the normal range
- Subjects with abnormal Vitamin D (Vitamin D, 25-Hydroxy) levels may be enroled if repeat lab results, obtained within 14 days of initial screening assessments, are within the normal range
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females.
- Lactating or pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test at screening or prior to dosing.
- The subject has participated in a clinical trial within 30 days or 5 half-lives of the IP prior to the first dosing day in the current study.
- Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Overland Park, Kansas, 66211
About this study
Official title: An Open Label, Single Center, Adaptive Phase I Study in Healthy Volunteers, to Evaluate the Safety, Efficacy and Dose Responses of SB-751689 (Ronacaleret; a Calcium Sensing Receptor Antagonist)
The present study aims to evaluate the impact of 5 days oral administration of ronacaleret 100 miligram (mg) and 400 mg on changes in circulating CD34+ cells, when ronacaleret is followed by the administration of a single dose of plerixafor in healthy human volunteers.
This single centre adaptive design study will be carried out in 2 parts. The part A will evaluate the change in peripheral circulating CD34+ cells in response to two different 5 day regimens of ronacaleret (100 mg or 400 mg once daily), given in conjunction with a single dose of plerixafor (0.24 mg/kilogram [kg]) sub-cutaneously (SC) on the evening of the final days dosing approximately 12 hours before collection of CD34+ cells on day 6. Subjects (5 each) will be assigned to either one of the ronacaleret arms, in an open fashion. Comparisons will be made in the change from baseline to end of treatment peripheral CD34+ cell counts. Part A will be conducted in two cohorts with 5 subjects being enrolled into each of the 2 treatment arms making up the first cohort. Cohort 2 will involve up to 5 further subjects being enrolled into each treatment arm.
Read more
The structure of part B will be finalized following a review of data generated in part A.
The total study duration of Part A for each subject including the screening, treatment and follow-up periods will be approximately 7 weeks.
- Conditions
- Transplantation, Stem Cell
- Being tested
- Ronacaleret 100 mg, Ronacaleret 400 mg, Plerixafor
- Keywords
- ronacaleret, parathyroid hormone (PTH), CD34+cells, calcium sensing receptor antagonist, hematopoietic stem cells, stem cell mobilization, plerixafor, healthy human volunteer, phase Ib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ronacaleret 100 mgDrug
Subjects in the Ronacaleret 100 mg group received one tablet orally of ronacaleret 100 mg for 5 consecutive days.
Ronacaleret 400 mgDrug
Subjects in the Ronacaleret 400 mg group received four tablets orally of ronacaleret 100 mg daily for 5 consecutive days.
PlerixaforDrug
Subjects in each group received a single dose of plerixafor (0.24mg/kg) SC on the evening of the Day 5 dosing approximately 12 hours before collection of CD34+ cells on day 6.
| Study group | Role | What they receive |
|---|---|---|
| Ronacaleret 100 mg | Experimental | Subjects will receive ronacaleret (100 mg once daily) for 5 consecutive days, given in conjunction with a single dose of plerixafor (0.24 mg/kg) SC on the evening of Day 5. Receives: Drug: Ronacaleret 100 mg; Drug: Plerixafor |
| Ronacaleret 400 mg | Experimental | Subjects will receive ronacaleret (400 mg once daily) for 5 consecutive days, given in conjunction with a single dose of plerixafor (0.24 mg/kg) SC on the evening of Day 5. Receives: Drug: Ronacaleret 400 mg; Drug: Plerixafor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change from baseline in CD34+ cell counts
The mean fold change from baseline in the number of circulating CD34+ cells for all treatment arms will be assessed. Samples will be collected at screening, Day 4 and Day 5 (2 hrs post ronacaleret dose), Day 6 (12 hrs and 14 and 16 hrs post plerixafor dose) and Day 14
Measured: Baseline and upto Day 14
Secondary outcomes (5)
Spontaneous AE reporting
Adverse events (AEs) will be collected from the start of Investigation Product (IP) and until the follow-up visit
Measured: Up to 14 days
Clinical laboratory safety data
Clinical laboratory tests will include hematology, clinical chemistry and urinalysis
Measured: Up to 14 days
Measure of vital signs to access safety and tolerability
Vital sign measurements will include systolic and diastolic blood pressure and pulse rate. Subjects should have been in a supine or semi-supine (recumbent) position for at least 5 minutes prior to taking measurements
Measured: Up to 14 days
PTH responses
Parathyroid hormone (PTH) has been shown to stimulate osteoblasts and osteoclasts and also associated with increased numbers of circulating CD34+ve cells
Measured: Up to 6 days
Quantification of the number of stem cells
The number of stem cells from the various hematopoietic lineages through colony forming unit assays in Part B of the study
Measured: Part B will be detailed in an amendment to the protocol following a data review of part A
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2013 (estimated)
- Study start2 Nov 2012
- Primary completion2 Apr 2013
- Study completion2 Apr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transplantation, Stem CellStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01802892
- Sponsor's protocol ID
- 116610
- Status last verified
- Jun 2017
- First submitted
- 1 Nov 2012
- Last updated
- 7 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single Center, Adaptive Phase I Study in Healthy Volunteers, to Evaluate the Safety, Efficacy and Dose Responses of SB-751689 (Ronacaleret; a Calcium Sensing Receptor Antagonist)
- ClinicalTrials.gov ID
- NCT01802892
- Acronym / sponsor ID
- 116610
- Conditions
- Transplantation, Stem Cell
- Keywords
- ronacaleret, parathyroid hormone (PTH), CD34+cells, calcium sensing receptor antagonist, hematopoietic stem cells, stem cell mobilization, plerixafor, healthy human volunteer, phase Ib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2012 (actual)
- Primary completion
- 2 Apr 2013 (actual)
- Study completion
- 2 Apr 2013 (actual)
- First posted
- 4 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study aims to evaluate the impact of 5 days oral administration of ronacaleret 100 miligram (mg) and 400 mg on changes in circulating CD34+ cells, when ronacaleret is followed by the administration of a single dose of plerixafor in healthy human volunteers.
This single centre adaptive design study will be carried out in 2 parts. The part A will evaluate the change in peripheral circulating CD34+ cells in response to two different 5 day regimens of ronacaleret (100 mg or 400 mg once daily), given in conjunction with a single dose of plerixafor (0.24 mg/kilogram [kg]) sub-cutaneously (SC) on the evening of the final days dosing approximately 12 hours before collection of CD34+ cells on day 6. Subjects (5 each) will be assigned to either one of the ronacaleret arms, in an open fashion. Comparisons will be made in the change from baseline to end of treatment peripheral CD34+ cell counts. Part A will be conducted in two cohorts with 5 subjects being enrolled into each of the 2 treatment arms making up the first cohort. Cohort 2 will involve up to 5 further subjects being enrolled into each treatment arm.
The structure of part B will be finalized following a review of data generated in part A.
The total study duration of Part A for each subject including the screening, treatment and follow-up periods will be approximately 7 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ronacaleret 100 mg | Experimental | Drug: Ronacaleret 100 mg, Drug: PlerixaforSubjects will receive ronacaleret (100 mg once daily) for 5 consecutive days, given in conjunction with a single dose of plerixafor (0.24 mg/kg) SC on the evening of Day 5. |
| Ronacaleret 400 mg | Experimental | Drug: Ronacaleret 400 mg, Drug: PlerixaforSubjects will receive ronacaleret (400 mg once daily) for 5 consecutive days, given in conjunction with a single dose of plerixafor (0.24 mg/kg) SC on the evening of Day 5. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- A male or female between 18 and 65 years of age (inclusive).
- Healthy as determined by a physician, based on a medical evaluation and with an estimated Glomerular Filtration Rate (GFR) of >=60 mL/min /1.73 m^2 using the four variable Modification of Diet in Renal Disease (MDRD) equation.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Female of non-child bearing potential, or female subjects and male subjects with female partners of child-bearing potential willing to use protocol-specified methods of contraception to prevent pregnancy during the study.
- Body weight of 55 kg or more and body mass index (BMI) of 20.0 to 35.0 kg/m^2 (inclusive).
Key exclusion criteria (15 listed)
- A positive pre-study drug/alcohol screen.
- A positive test for HIV, B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- History of or therapy for osteoporosis
- Subject has had treatment for any condition relating to the thyroid/parathyroid gland which in the opinion of the investigator may influence the subjects production of PTH
- Subjects with any contraindications or know allergies to receiving plerixafor
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 |
|---|---|---|
| Ronacaleret 100 mgSubjects in the Ronacaleret 100 mg group received one tablet orally of ronacaleret 100 mg for 5 consecutive days. | Drug | Ronacaleret 100 mg |
| Ronacaleret 400 mgSubjects in the Ronacaleret 400 mg group received four tablets orally of ronacaleret 100 mg daily for 5 consecutive days. | Drug | Ronacaleret 400 mg |
| PlerixaforSubjects in each group received a single dose of plerixafor (0.24mg/kg) SC on the evening of the Day 5 dosing approximately 12 hours before collection of CD34+ cells on day 6. | Drug | Ronacaleret 100 mg, Ronacaleret 400 mg |
Primary outcome
Mean change from baseline in CD34+ cell counts
Time frame: Baseline and upto Day 14
The mean fold change from baseline in the number of circulating CD34+ cells for all treatment arms will be assessed. Samples will be collected at screening, Day 4 and Day 5 (2 hrs post ronacaleret dose), Day 6 (12 hrs and 14 and 16 hrs post plerixafor dose) and Day 14
5 secondary outcomes
Spontaneous AE reporting
Time frame: Up to 14 days
Clinical laboratory safety data
Time frame: Up to 14 days
Measure of vital signs to access safety and tolerability
Time frame: Up to 14 days
PTH responses
Time frame: Up to 6 days
Quantification of the number of stem cells
Time frame: Part B will be detailed in an amendment to the protocol following a data review of part A
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
- Results for study 116610 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ronacaleret 100 mg, Ronacaleret 400 mg and Plerixafor in people with Transplantation, Stem Cell, run by GlaxoSmithKline at 1 site in United States.
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 6 inclusion and 15 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 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Mean change from baseline in CD34+ cell counts (time frame: Baseline and upto Day 14). 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 7 Jun 2017.