A Study to Evaluate the Effects of SB-751689 or rhPTH(1-34) on Excretion of Calcium and Phosphate in Women
A Study to Evaluate the Effects of SB-751689 or rhPTH(1-34) on Excretion of Calcium and Phosphate in Women
SB-751689 may alter calcium and phosphate handling at the kidney level. This study will
 examine what happens to calcium and phosphate, and other electrolytes, at the kidney after
 treatment with SB-751689 for 1 month. Another group of subjects will get another drug called
 Forteo for 1 month to compare the response of the kidney for calcium and phosphate.
Inclusion Criteria:

 -  Healthy postmenopausal women 40 to 65 years of age, inclusive, meeting at least one of
 the following: Postmenopausal defined by the STRAW criteria of 12 months of
 spontaneous amenorrhea with serum FSH levels = 40 mIU/mL; History of bilateral
 oophorectomy (with or without hysterectomy) and at least 6 weeks post-surgical with
 serum FSH levels = 40 mIU/mL

 -  Body weight > 50 kg and BMI within the range 19 - 32 kg/m2

 -  Capable of giving written informed consent

 Exclusion Criteria:

 -  Any clinically relevant biological or physical abnormality found or reported at
 screening which, in the opinion of the investigator, is clinically significant and
 would preclude safe participation in this study. These abnormalities may be identified
 on the screening history and physical or laboratory examination and 12-lead
 electrocardiogram (ECG).

 -  A subject may not participate in the study if any of the following laboratory results
 are above the upper limit of the normal range at screening: liver function tests (ALT,
 AST, GGT, alkaline phosphatase, total bilirubin), plasma amylase, glucose, alkaline
 phosphatase, or CPK.

 -  A subject may not participate in the study if any of the following laboratory results
 are outside the normal range at screening: serum levels of albumin-adjusted calcium,
 total calcium, PTH, and urinary calcium.

 -  A subject with vitamin D deficiency as defined by serum 25-hydroxy vitamin D < 20
 ng/mL (equivalent to 50 nmol/L) at screening may not participate in the study. A QTc
 interval > 450 msec at screening.

 -  Positive urine drug screen.

 -  Positive for HIV, hepatitis B virus or hepatitis C virus assays.

 -  Urinary cotinine levels indicative of smoking.

 -  History of smoking or use of nicotine containing products within one year of
 screening.

 -  History of regular alcohol consumption

 -  History of drug abuse within 6 months of the study.

 -  Participation in a study with an investigational drug within 30 days or 5 half-lives
 (whichever is longer) preceding the first dose of study medication.

 -  Exposure to more than four new chemical entities within 12 months prior to the first
 dosing day.

 -  Use of prescription or non-prescription drugs, calcium containing antacids, aspirin or
 nonsteroidal anti-inflammatory drugs, vitamins, herbal and dietary supplements,
 excluding study related vitamin D and calcium supplements, within 14 days prior to the
 first dose of study medication.

 -  Donation of blood in excess of 500 mL within 56 days prior to dosing.

 -  Evidence of hepatic or biliary disease (including cholecystectomy and Gilbert's
 Syndrome).

 -  Significant renal disease as define by:

 -  Serum creatinine clearance <60ml/min (estimated from serum creatinine (SCr) and
 demographic data using the MDRD calculation):

 -  A validated web-based calculator is found at:
 http://nephron.com/cgi-bin/MDRDSIdefault.cgi

 -  GFR Calculator

 -  To calculate estimated GFR (mL/min/1.73m2) manually:

 -  = 186 x (SCr in mg/dL)-1.154 x (age)-0.203 x (0.742 if female) x (1.210 if
 African-American)

 -  = exp(5.228-1.154 x ln (SCr)-0.203x ln(age)-(0.299 if female) + (0.192 if African
 American))

 -  Urine protein/creatinine (mg/mg) ratio >2.5; or urine albumin concentration > 300
 ug/mg.

 -  Known loss of kidney, either surgically or by injury or disease

 -  History of significant gastrointestinal

 -  History of a gastrointestinal surgical procedure that might affect the absorption of
 SB-751689

 -  History of sensitivity to any of the study medications or components thereof.

 -  History of clinically significant cardiovascular disease.

 -  History of pancreatitis or kidney stones. Medical conditions which might alter bone
 metabolism

 -  Subjects at increased risk of osteosarcoma such as those with Paget's disease of the
 bone or any prior external beam or implant radiation therapy involving the skeleton.