Official Title: “A Two-Part Dose-Rising Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SB-751689 When Administered as an Oral Formulation at Supratherapeutic Dose Levels in Healthy Adult Subjects.”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind, Placebo Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2007

Intervention(s) in this Clinical Trial

• Drug: SB-751689 oral tablets (100 and 400 ng)
• Drug: Ketoconazole (NIZORAL) oral tablets (200 mg)

Primary Measures

• 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
  • Time Frame: throughout the study
    

Secondary Measures

• 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.
  • Time Frame: throughout the study
    

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: GlaxoSmithKline

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, MD Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00468689

Study ID Number: CR9107262

ClinicalTrials.gov Identifier: NCT00468689

Health Authority: United States: Food and Drug Administration