A Study to Investigate the Interaction of GSK1292263 With Rosuvastatin and Simvastatin in Healthy Subjects

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Study to Investigate the Interaction of GSK1292263 With Rosuvastatin and Simvastatin in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01101568
• Other study ID #: 113506
• Status: Completed
• Phase: Phase 1
• First received: April 8, 2010
• Last updated: June 12, 2017
• Start date: April 14, 2010
• Est. completion date: June 24, 2010

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a Phase I, open-label, single-sequence drug interaction study to evaluate the effect of repeated doses of GSK1292263 on the pharmacokinetics of rosuvastatin and simvastatin in healthy adult subjects. Each subject will receive single doses of simvastatin and rosuvastatin on two occasions, once alone and once following administration of repeated (BID) doses of GSK1292263.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 24, 2010
• Est. primary completion date: June 24, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• 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.

• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.

• A female subject is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or bilateral oophorectomy or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. If the clinical situation is unclear, FSH and estradiol levels may be used to confirm post-menopausal status at Screening. Simultaneous follicle stimulating hormone (FSH) > 40 mIU/ml and estradiol < 40pg/ml (<140pmol/L) is confirmatory in the absence of a clear post-menopausal history.

• Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 5 terminal half-lives (i.e. 4 days) post-last dose.

• Body weight greater than or equal to 50 kg and BMI within the range 19 - 30 kg/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 Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

• A positive pre-study drug/alcohol screen.

• A positive test for HIV antibody.

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Subjects with cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to Screening are excluded.

• Gastrointestinal disease that could affect fat or bile acid absorption, or the pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory bowel disease, chronic diarrhea, Crohn's or malabsorption syndromes within the past year

• Gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs

• Subjects may be enrolled in the study if they have had a cholecystectomy three or more months before the time of screening and are stable and asymptomatic.

• Significant ECG abnormalities, defined in the protocol. Subjects with Left Bundle Branch Block are excluded from the study. Subjects with partial Right Bundle Branch Block may be considered for inclusion following consultation with the GSK Medical Monitor. Subjects with WPW syndrome are excluded from the study.

• 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).

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

• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.

• Lactating females.

• Unwillingness or inability to follow the procedures outlined in the protocol.

• Subject is mentally or legally incapacitated.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

• Subjects who have asthma or a history of asthma, (e.g., for any FTIH where risk of bronchoconstriction is unknown, or compound specific where risk of bronchoconstriction).

• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

• Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.

• CPK above the upper limit of normal at screening.

• Lactose intolerance.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Simvastatin
Simvastatin 40mg (single dose) on Days 1 and 10.
• Rosuvastatin
Rosuvastatin 10mg (single dose) on Days 3 and 12.
• GSK1292263
GSK1292263 300mg BID Days 6 to 14.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC(0-inf) and Cmax of rosuvastatin alone and in the presence of GSK1292263		Day 3 and Day 12
Primary	AUC(0-inf) and Cmax of simvastatin/simvastatin acid alone and in the presence of GSK1292263		Day 1 and Day 10
Secondary	Safety and tolerability: adverse events, cardiovascular findings (blood pressure, heart rate, ECGs) and clinical laboratory values.		Throughout the study (Day 1 to Day 25)
Secondary	PK parameters: time to maximum plasma concentration, apparent plasma terminal elimination half-life and area under the plasma concentration-time curve for rosuvastatin [AUC(0-72 hours)] and simvastatin/simvastatin acid [AUC(0-24h)]		15 days
Secondary	PK parameter values: AUC(0-24h), Cmax, tmax and t1/2 for GSK1292263 and assessment of steady-state		From Day 6 to Day 15

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 113506 can be found on the GSK Clinical Study Register.