A Two Cohort Study to Look at the Metabolites of GSK221149, the Metabolism of GSK221149 Administered With a High Fat Meal and With Ketoconazole

NCT ID: NCT01627587

Last Updated: 2017-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-12
• Study Completion Date: 2012-02-09

Brief Summary

This is a two part study. Part A of the study will evaluate the metabolites of GSK221149 following single and repeat oral dosing and will also assess the pharmacokinetics of GSK221149 when administered with a potent CYP3A4 inhibitor Ketoconazole. Part B of the study will look at the pharmacokinetics of GSK221149 following a high fat meal.

Conditions

Obstetric Labour, Premature

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Ketoconazole-Part A

Healthy Female volunteers of child bearing potential will receive Treatment A, B and C

Group Type: EXPERIMENTAL

GSK221149 750 mg

Intervention Type: DRUG

Treatment A: 750 mg GSK221149 single dose

Ketoconazole

Intervention Type: DRUG

Treatment B: 400 mg of Ketoconazole single dose

GSK221149 100 mg

Intervention Type: DRUG

Treatment C: 100mg of GSK221149 single dose

Food-Part B

Healthy Female Volunteers of child bearing potential will receive Treament D and E

Group Type: EXPERIMENTAL

GSK221149 750 mg Fasted

Intervention Type: DRUG

Treatment D: 750 mg of GSK221149 administered fasted

GSK221149 750 mg + Food

Intervention Type: DRUG

Treatment E: 750 mg of GSK221149 administered with a high fat meal

Interventions

GSK221149 750 mg

Treatment A: 750 mg GSK221149 single dose

Intervention Type: DRUG

Ketoconazole

Treatment B: 400 mg of Ketoconazole single dose

Intervention Type: DRUG

GSK221149 100 mg

Treatment C: 100mg of GSK221149 single dose

Intervention Type: DRUG

GSK221149 750 mg Fasted

Treatment D: 750 mg of GSK221149 administered fasted

Intervention Type: DRUG

GSK221149 750 mg + Food

Treatment E: 750 mg of GSK221149 administered with a high fat meal

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
• Single [QTc, QTcB or QTcF] less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.
• 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.
• Female subjects between 18 and 45 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of: Child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 48 hours post last dose.
• Body weight greater than 50 kg and BMI within the range 19-29.9 kg/m2 (inclusive).

Exclusion Criteria

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol/urine cotinine screen.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 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.
• Unable to refrain from the 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 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.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummels, exotic citrus fruits, grapefruit hybrids from 7 days prior to the first dose of study medication.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Austin, Texas, United States

Countries

United States

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

115893

Identifier Type: -

Identifier Source: org_study_id