Evaluation Of SB-751689 Administered At Supratherapeutic Dose Levels In Healthy Adult Subjects.

Osteoporosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468689
• Other study ID #: CR9107262
• Status: Completed
• Phase: Phase 1
• First received: May 1, 2007
• Last updated: October 9, 2008
• Start date: April 2007
• Est. completion date: August 2007

Study information

• Verified date: October 2008
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• SB-751689 oral tablets (100 and 400 ng)

• Ketoconazole (NIZORAL) oral tablets (200 mg)

Locations

Country	Name	City	State
United States	GSK Investigational Site	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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