An Adaptive Phase I Study to Evaluate the Safety, Efficacy and Dose Responses of Ronacaleret in Healthy Human Volunteers

Inclusion Criteria: * 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 Exclusion Criteria: * 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 * 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