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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ronacaleret 100 mg | Drug | Subjects in the Ronacaleret 100 mg group received one tablet orally of ronacaleret 100 mg for 5 consecutive days. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline and upto Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Spontaneous AE reporting | Adverse events (AEs) will be collected from the start of Investigation Product (IP) and until the follow-up visit | Up to 14 days |
| Clinical laboratory safety data | Clinical laboratory tests will include hematology, clinical chemistry and urinalysis |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
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| Label | URL |
|---|---|
| Results for study 116610 can be found on the GSK Clinical Study Register. | View source |
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| ID | Term |
|---|---|
| C561716 | ronacaleret |
| C088327 | plerixafor |
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| Ronacaleret 400 mg | Drug | Subjects in the Ronacaleret 400 mg group received four tablets orally of ronacaleret 100 mg daily for 5 consecutive days. |
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| Plerixafor | Drug | 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. |
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| 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 | 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 | 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 | Part B will be detailed in an amendment to the protocol following a data review of part A |