Osteoporosis
Conditions
Keywords
SB-751689,, Calcium-sensing receptor antagonist (CaR),, Osteoporosis,, Parathyroid hormone (PTH),, Oral dose
Brief summary
This study will evaluate the safety, tolerability and exposure of SB-751689 when administered alone at supratherapeutic doses and when SB-751689 is co administered with ketoconazole, a PGP/CYP3A4 inhibitor that increases exposure of SB-751689. Data from this study will enable the planning and conduct of a QTc study for SB-751689.
Interventions
DRUGSB-751689 oral tablets (100 and 400 ng)
DRUGKetoconazole (NIZORAL) oral tablets (200 mg)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults aged 18-60yrs, with BMI of 19-31kg/m2. * Females must be of non-childbearing potential. * Subjects must be able to give consent and comply with restrictions of study.
Exclusion criteria
* Clinically relevant abnormality from history, physical, 12-lead ECG, Holter monitoring, or clinical laboratory examination. * Positive urine drug screen. * Positive urine test for alcohol. * Contine levels indicative of smoking. * Positive HIV or Hep B and/or C assay. * History or smoking in last year or \>10 pack/year history of smoking overall. * History of regular alcohol consumption (7 units/week for women and 14 units/week for men) within 6 months of study. * History of drug abuse within 6 months of study. * Participation in another drug trial within 30 days of first dose. * Exposure to more than 4 new chemical entities within 12 months of first dose. * Use of prescription and non-prescription drugs including dietary supplements, herbals and St. John's wort within 14 days of first dose. * Consumption of red wine, grapefruit, grapefruit juice and grapefruit products within 14 days of first dose. * Donation of blood in excess of 500 mL within 56 days of dosing. * Evidence of renal, hepatic or biliary impairment. * History of serious gastrointestinal disease or history of gastrointestinal surgical procedure that might affect absorption of study drug. * History of sensitivity to any of the study medications. * History of clinically significant cardiovascular disease. * History of pernicious anemia, pancreatitis, osteosarcoma or kidney stones. Medical conditions which might alter bone metabolism. * Liver function tests above ULN at screening and PTH, glucose, and CPK outside the reference range at screening. * Males unwilling to refrain from fathering a child during the study and for 14 days following the last dose of study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of SB-751689 doses determined from clinical safety and tolerability data from all adverse event reporting, 12-lead ECGs, vital signs, nursing/physician observation, and safety laboratory tests | throughout the study |
Secondary
| Measure | Time frame |
|---|---|
| PK and of SB-751689 as determined by AUC, Cmax, tmax, and half-life. PD effects (PTH, serum Ca) as determined by AUC, Emax, tmax, maximum change and % change from baseline, duration of effect, duration above ULN for PTH. | throughout the study |
Countries
United States
Outcome results
None listed