Clinical trial NCT00468689: Evaluation Of SB-751689 Administered At Supratherapeutic Dose Levels In Healthy Adult Subjects.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoporosis
Keywords: SB-751689,
Calcium-sensing receptor antagonist (CaR),
Osteoporosis,
Parathyroid hormone (PTH),
Oral dose
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-05-03
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: throughout the study
Secondary outcomes:
measure: 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.
timeFrame: throughout the study
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials, MD
role: STUDY_DIRECTOR
References: