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

NCT01627587 | Completed Phase 1

• 1 other identifier: 115893
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

Keywords

preterm labor

Outcome Measures

Primary Outcomes (2)

• Area under the curve, half life

  From Day 1- Day 11 of the study

• Area under the curve, half life, when treate with ketconizole

  Day 1-11

Secondary Outcomes (1)

• 12 lead ECGs, safety labs, vital signs, heart rate, blood pressure

  Day 1- Day 11 of the study

Study Arms (2)

Ketoconazole-Part A

EXPERIMENTAL

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

Drug: GSK221149 750 mg; Drug: Ketoconazole; Drug: GSK221149 100 mg

Food-Part B

EXPERIMENTAL

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

Drug: GSK221149 750 mg Fasted; Drug: GSK221149 750 mg + Food

Interventions

GSK221149 750 mg DRUG

Treatment A: 750 mg GSK221149 single dose

Ketoconazole-Part A

Ketoconazole DRUG

Treatment B: 400 mg of Ketoconazole single dose

Ketoconazole-Part A

GSK221149 100 mg DRUG

Treatment C: 100mg of GSK221149 single dose

Ketoconazole-Part A

GSK221149 750 mg Fasted DRUG

Treatment D: 750 mg of GSK221149 administered fasted

Food-Part B

GSK221149 750 mg + Food DRUG

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

Food-Part B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Links

• Results for study 115893 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Premature Birth; Obstetric Labor, Premature

Interventions

Ketoconazole; Food

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 26, 2012
• Study Start: December 12, 2011
• Primary Completion: February 9, 2012
• Study Completion: February 9, 2012
• Last Updated: June 15, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)