Bone Marrow TransplantationPhase 1NCT01466335
An Adaptive Phase I Study to Evaluate the Safety, Efficacy and Dose Responses of Ronacaleret in Healthy Human Volunteers
A Phase 1 study testing Ronacaleret (100mg tablet) in people with Bone Marrow Transplantation, run by GlaxoSmithKline at 1 site in United States.
Trial summary
Ronacaleret is an orally administered CaSR antagonist which has previously been demonstrated to transiently increase PTH in both animals and humans. Additional studies in post-menopausal women and patients with distal radial fractures have demonstrated both anabolic and catabolic effects on bone biomarkers and scans… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Bone Marrow Transplantation
- What is being tested?
- Ronacaleret (100mg tablet)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Oct 2011to 5 Mar 2012
- 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
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with serum Ca values outside the normal range should always be excluded from enrollment
- Estimated GFR greater than or equal to 60 ml/min/1.73 m2 using the MDRD formula
- AST, ALT, alkaline phosphatase and bilirubin > 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- A female subject is eligible to participate if she is of non-childbearing potential or is of child-bearing potential and agrees to use one of the contraception methods stipulated in the protocol
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol
- Body weight greater than or equal to 55 kg and BMI within the range 20 - 35kg/m2 (inclusive)
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Who cannot join
- A positive pre-study HIV, B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones)
- History of or therapy for osteoporosis
- Subjects taking calcium and/or vitamin D supplements, during or within 2 weeks of study initiation
- Serum calcium (total or albumin-adjusted) outside the central laboratory reference range at the screening visit
- PTH outside the normal range at the screening visit
Show all 13Show fewer
- Creatine phosphokinase (CPK) outside the normal range at the screening visit
- A positive pre-study drug/alcohol screen
- 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. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
- Lactating or pregnant females as determined by positive [serum or urine] hCG test at screening or prior to dosing
- Subject is unwilling to refrain from the consumption of red wine, Seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication until the study visits are complete
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double Blind, Parallel Group, Single Center, Adaptive Phase I Study to Evaluate the Safety, Efficacy and Dose Responses of SB-751689 (Ronacaleret; a Calcium Sensing Receptor Antagonist) for Durations Not to Exceed 28 Days, Versusplacebo in Healthy Human Volunteers.
Ronacaleret is an orally administered CaSR antagonist which has previously been demonstrated to transiently increase PTH in both animals and humans. Additional studies in post-menopausal women and patients with distal radial fractures have demonstrated both anabolic and catabolic effects on bone biomarkers and scans of bone density. Based on ronacalerets ability to interact with the CaSR inducing PTH release and activating endogenous bone metabolism of both osteoblasts and osteoclasts, it is our intention to evaluate the impact activation of this pathway has on mobilization of Hematopoietic stem cell (HSCs) into the periphery.
This is an adaptive, phase I, randomized, single centre, double-blind dose finding, parallel-group, multi-cohort placebo controlled study of the efficacy and safety of ronacaleret in up to 45 healthy human volunteers. Cohorts of eligible subjects will be studied for periods up to 28 days. Total daily doses of ronacaleret will range from 100mg, up to 400mg and be administered for a maximum of 28days. The first part of this study will evaluate several doses and schedules of ronacaleret, run in parallel, with respect to their ability to affect mobilization of CD34+ cells into the peripheral circulation. In subsequent cohorts of the study we will utilize information obtained from previous cohorts to further refine and optimise those dosing paradigms which show efficacy. For the first cohort of study participants; the study will commence with 6 days of dosing in an inpatient setting followed by 21 days of continued dosing and evaluation as an outpatient, with a series of regularly scheduled visits, with the final visit on day 28. The study period will include evaluations of pharmacokinetic and pharmacodynamic parameters along with standard laboratory and safety evaluations. The second cohort may be treated with ronacaleret for periods ranging from 14 to 28 days in order to optimise the treatment paradigm with respect to pharmacodynamic efficacy. The PK/PD of each group in cohort one will be utilized to make adjustments in the total daily dose, dose frequency and or duration of dosing investigated in cohort 2. Decisions will be made as to dropping doses based on the PK/PD results and any safety considerations. An initial equal randomization amongst groups within the first cohort may be adjusted to allow for other randomization strategies as various doses and schedules are assessed.
The objective of this study is to characterise the dose-response curve for ronacaleret with respect to safety and efficacy based on changes in peripheral CD34+ cell counts. Results obtained from this study will inform us: of optimized doses, schedules, and durations of treatment for future studies. Additional cohorts may be added to further explore the dose schedule and duration if required. The exact number of cohorts studied will depend on the results obtain from the prior groups and the desire to explore a variety of doses and schedules. The aims of the present study (CR9115166) include an assessment of the pharmacodynamic effects (mobilization of CD34+ cells), safety, tolerability, and pharmacokinetics of ronacaleret in healthy human volunteers.
- Conditions
- Bone Marrow Transplantation
- Being tested
- Ronacaleret (100mg tablet), Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ronacaleret (100mg tablet)Drug
100mg tablet
PlaceboDrug
matching placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Ronacaleret 100mg once daily | Experimental | 1 x 100mg oral tablet Receives: Drug: Ronacaleret (100mg tablet) |
| Ronacaleret 100mg twice daily | Experimental | 1 x 100mg oral tablet twice daily Receives: Drug: Ronacaleret (100mg tablet) |
| Ronacaleret 200mg once daily | Experimental | 2 x 100mg oral tablet Receives: Drug: Ronacaleret (100mg tablet) |
| Ronacaleret 200mg twice daily | Experimental | 2 x 100mg tablets twice daily Receives: Drug: Ronacaleret (100mg tablet) |
| Ronacaleret 400mg once daily | Experimental | 4 x 100mg tablets Receives: Drug: Ronacaleret (100mg tablet) |
| Placebo | Placebo comparator | Matching number of identical placebo tablets Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
assess the mean fold increase in the number of peripheral CD34+ cells, at total daily doses ranging from 100mg to 400mgs over 1 to 28 days
Measured: 1-28 days
Secondary outcomes (7)
Determine the peak CD34+ cell mobilization kinetics
Measured: 1-28 days
Adverse Events (AE's)
Measured: 1-28 days
optimum dosing frequency respect to mean fold increases in the number of CD34+ cells/kg mobilized
Measured: 1-28 days
optimum duration of dosing (ranging from single dose to 28 days) of ronacaleret with respect to mean fold increases in the number of CD34+ cells/kg mobilized
Measured: 1-28 days
cardiovascular parameters (12-lead ECG, heart rate, blood pressure)
Measured: 1-28 days
clinical chemistry and hematology parameters
Measured: 1-28 days
Population pharmacokinetic parameters of GSK962040: Cmax, Tmax, AUC(0-t), Ct, CL/F, V/F, and, if possible, half-life
Measured: 1-28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2011 (estimated)
- Study start27 Oct 2011
- Primary completion5 Mar 2012
- Study completion5 Mar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Marrow TransplantationStudies 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 39 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
- NCT01466335
- Sponsor's protocol ID
- 115166
- Status last verified
- Jun 2017
- First submitted
- 27 Oct 2011
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Parallel Group, Single Center, Adaptive Phase I Study to Evaluate the Safety, Efficacy and Dose Responses of SB-751689 (Ronacaleret; a Calcium Sensing Receptor Antagonist) for Durations Not to Exceed 28 Days, Versusplacebo in Healthy Human Volunteers.
- ClinicalTrials.gov ID
- NCT01466335
- Acronym / sponsor ID
- 115166
- Conditions
- Bone Marrow Transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 27 Oct 2011 (actual)
- Primary completion
- 5 Mar 2012 (actual)
- Study completion
- 5 Mar 2012 (actual)
- First posted
- 7 Nov 2011 (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.
Ronacaleret is an orally administered CaSR antagonist which has previously been demonstrated to transiently increase PTH in both animals and humans. Additional studies in post-menopausal women and patients with distal radial fractures have demonstrated both anabolic and catabolic effects on bone biomarkers and scans of bone density. Based on ronacalerets ability to interact with the CaSR inducing PTH release and activating endogenous bone metabolism of both osteoblasts and osteoclasts, it is our intention to evaluate the impact activation of this pathway has on mobilization of Hematopoietic stem cell (HSCs) into the periphery.
This is an adaptive, phase I, randomized, single centre, double-blind dose finding, parallel-group, multi-cohort placebo controlled study of the efficacy and safety of ronacaleret in up to 45 healthy human volunteers. Cohorts of eligible subjects will be studied for periods up to 28 days. Total daily doses of ronacaleret will range from 100mg, up to 400mg and be administered for a maximum of 28days. The first part of this study will evaluate several doses and schedules of ronacaleret, run in parallel, with respect to their ability to affect mobilization of CD34+ cells into the peripheral circulation. In subsequent cohorts of the study we will utilize information obtained from previous cohorts to further refine and optimise those dosing paradigms which show efficacy. For the first cohort of study participants; the study will commence with 6 days of dosing in an inpatient setting followed by 21 days of continued dosing and evaluation as an outpatient, with a series of regularly scheduled visits, with the final visit on day 28. The study period will include evaluations of pharmacokinetic and pharmacodynamic parameters along with standard laboratory and safety evaluations. The second cohort may be treated with ronacaleret for periods ranging from 14 to 28 days in order to optimise the treatment paradigm with respect to pharmacodynamic efficacy. The PK/PD of each group in cohort one will be utilized to make adjustments in the total daily dose, dose frequency and or duration of dosing investigated in cohort 2. Decisions will be made as to dropping doses based on the PK/PD results and any safety considerations. An initial equal randomization amongst groups within the first cohort may be adjusted to allow for other randomization strategies as various doses and schedules are assessed.
The objective of this study is to characterise the dose-response curve for ronacaleret with respect to safety and efficacy based on changes in peripheral CD34+ cell counts. Results obtained from this study will inform us: of optimized doses, schedules, and durations of treatment for future studies. Additional cohorts may be added to further explore the dose schedule and duration if required. The exact number of cohorts studied will depend on the results obtain from the prior groups and the desire to explore a variety of doses and schedules. The aims of the present study (CR9115166) include an assessment of the pharmacodynamic effects (mobilization of CD34+ cells), safety, tolerability, and pharmacokinetics of ronacaleret in healthy human volunteers.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Ronacaleret 100mg once daily | Experimental | Drug: Ronacaleret (100mg tablet)1 x 100mg oral tablet |
| Ronacaleret 100mg twice daily | Experimental | Drug: Ronacaleret (100mg tablet)1 x 100mg oral tablet twice daily |
| Ronacaleret 200mg once daily | Experimental | Drug: Ronacaleret (100mg tablet)2 x 100mg oral tablet |
| Ronacaleret 200mg twice daily | Experimental | Drug: Ronacaleret (100mg tablet)2 x 100mg tablets twice daily |
| Ronacaleret 400mg once daily | Experimental | Drug: Ronacaleret (100mg tablet)4 x 100mg tablets |
| Placebo | Placebo comparator | Drug: PlaceboMatching number of identical placebo tablets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with serum Ca values outside the normal range should always be excluded from enrollment
- Estimated GFR greater than or equal to 60 ml/min/1.73 m2 using the MDRD formula
- AST, ALT, alkaline phosphatase and bilirubin > 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- A female subject is eligible to participate if she is of non-childbearing potential or is of child-bearing potential and agrees to use one of the contraception methods stipulated in the protocol
Key exclusion criteria (13 listed)
- A positive pre-study HIV, B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones)
- History of or therapy for osteoporosis
- Subjects taking calcium and/or vitamin D supplements, during or within 2 weeks of study initiation
- Serum calcium (total or albumin-adjusted) outside the central laboratory reference range at the screening visit
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 (100mg tablet)100mg tablet | Drug | Ronacaleret 100mg once daily, Ronacaleret 100mg twice daily, Ronacaleret 200mg once daily, Ronacaleret 200mg twice daily, Ronacaleret 400mg once daily |
| Placebomatching placebo tablet | Drug | Placebo |
Primary outcome
assess the mean fold increase in the number of peripheral CD34+ cells, at total daily doses ranging from 100mg to 400mgs over 1 to 28 days
Time frame: 1-28 days
7 secondary outcomes
Determine the peak CD34+ cell mobilization kinetics
Time frame: 1-28 days
Adverse Events (AE's)
Time frame: 1-28 days
optimum dosing frequency respect to mean fold increases in the number of CD34+ cells/kg mobilized
Time frame: 1-28 days
optimum duration of dosing (ranging from single dose to 28 days) of ronacaleret with respect to mean fold increases in the number of CD34+ cells/kg mobilized
Time frame: 1-28 days
cardiovascular parameters (12-lead ECG, heart rate, blood pressure)
Time frame: 1-28 days
clinical chemistry and hematology parameters
Time frame: 1-28 days
Population pharmacokinetic parameters of GSK962040: Cmax, Tmax, AUC(0-t), Ct, CL/F, V/F, and, if possible, half-life
Time frame: 1-28 days
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 20 Jun 2017.
- Results for study 115166 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Related trials for Bone Marrow Transplantation
RecruitingPhase 2
Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases
Acute Leukemia of Ambiguous Lineage, Acute Lymphoblastic Leukemia
RecruitingPhase 2
Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
Primary T-cell Immunodeficiency Disorders, Common Variable Immunodeficiency
Active, not recruitingPhase 2
Cord Blood Transplant in Adults With Blood Cancers
Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia (ALL)
RecruitingPhase 1
A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant
Accelerated Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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 (100mg tablet) in people with Bone Marrow Transplantation, 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 8 inclusion and 13 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 20 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. Some participants in this study may receive a placebo. 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?
assess the mean fold increase in the number of peripheral CD34+ cells, at total daily doses ranging from 100mg to 400mgs over 1 to 28 days (time frame: 1-28 days). 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 20 Jun 2017.