Expired Study
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Buffalo, New York 14202


Purpose:

This study is meant to assess potential inhibitory effects of GSK376501 on CYP450 isoenzymes 3A4, 2C8, 2C9. subjects will receive probe compounds and systemic levels of these substrates will be compared pre and post dosing of GSK376501.


Criteria:

Inclusion Criteria: - Healthy as determined by a qualified 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 considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. - Male or female between 18 and 55 years of age. - A female subject is eligible to participate if she is of non-childbearing potential, defined as: a. pre-menopausal females with a documented tubal ligation or hysterectomy; or b. postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. - Body weight ≥ 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. - Demonstrates an average QTc interval < 450 msec (or < 480 msec in subjects with bundle branch block), an average PR interval < 200 msec, and a QRS duration < 110msec (manual or machine read) at screening or baseline Exclusion Criteria: - A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. - A positive test for HIV antibody. - 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. - Previous exposure to GSK376501. - Unwillingness or inability to follow the procedures outlined in the protocol. - Demonstrates symptomatic or asymptomatic arrhythmia of any clinical significance during screening. - The subject has a positive pre-study drug/alcohol screen and is unwilling to abstain from 72 hours prior to dose until follow-up. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. - Urinary cotinine levels indicative of smoking or history or use of tobacco or nicotine-containing products within 6 months prior to screening. - Has a history of alcohol abuse or dependence within 12 months prior to the study. Alcohol abuse is defined as an average consumption of greater than 7 drinks per week for women or greater than 14 drinks per week for men. One alcohol drink is defined as the equivalent of 12 g of alcohol as follows: 5 oz/150 ml wine, 12 oz (360 ml) beer or 1.5 oz (45 ml) of 80 proof distilled spirits. - Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort, kava, ephedra [ma huang], gingko biloba, DHEA, vohimbe, saw palmetto, ginseng, red yeast rice) 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 and is unwilling to abstain from use of these medications until the last pharmacokinetic or pharmacodynamic sample has been collected, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. - Use of caffeine- or xanthine-containing products for 24 hours prior to dose until the last pharmacokinetic sample has been collected. - Consumption of any food or any beverage containing (alcohol, grapefruit or - grapefruit juice, apple or orange juice, Seville oranges, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats). from 7 days prior to the first dose of study medication. - Use of acetaminophen within 48 hours of the first dose and is unable or unwilling to discontinue use of acetaminophen until the last pharmacokinetic sample has been collected. - Use of aspirin, aspirin-containing compounds, salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours days of the first dose and is unwilling to abstain from use of these medications until the last pharmacokinetic sample has been collected. - Use of liquid antacids (e.g. Maalox, Mylanta, Amphogel, milk of magnesia) or chewable antacids (e.g. TUMS™) within 48 hours of the first dose and is unwilling to abstain from use of these medications until the last dose of study medication. - 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. - Alkaline phosphatase value higher than 1.5 times the upper limit of normal at screening or at baseline. - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct (conjugated) bilirubin, or CPK values higher than 1.25 times upper limit of normal at screening or at baseline. - Fasting triglyceride level > 400 mg/dL (4.52 mmol/L) at screening or at baseline. Triglyceride levels within a 10% margin above this level will be considered on a case-by-case basis. - Donation of blood or blood products in excess of 500 mL within a 56 day period. - History of sensitivity to heparin or heparin-induced thrombocytopenia. - History of or current congestive heart failure (NYHA Class I-IV symptoms) - History of thyroid dysfunction or an abnormal thyroid function test as assessed by TSH as screening.


Study is Available At:


Original ID:

DIX110825


NCT ID:

NCT00615212


Secondary ID:


Study Acronym:


Brief Title:

Effect of GSK376501 on CYP450 Activity in Healthy Adult Subjects


Official Title:

A Single Center, Single Sequence, Open-Label, Repeat-Dose Study to Investigate the Effect of GSK376501 on Hepatic Cytochrome P450 Activity in Healthy Adult Subjects


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

55 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

GlaxoSmithKline


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

7


Number of Groups:

0


Total Enrollment:

23


Enrollment Type:

Actual


Overall Contact Information

Official Name:GSK Clinical Trials
Study Director
GlaxoSmithKline

Study Dates

Start Date:January 2, 2008
Completion Date:February 15, 2008
Completion Type:Actual
Primary Completion Date:February 15, 2008
Primary Completion Type:Actual
Verification Date:September 2017
Last Changed Date:September 8, 2017
First Received Date:February 1, 2008

Study Outcomes

Outcome Type:Primary Outcome
Measure:drug plasma levels midazolam:
Time Frame:Days 1 & 11
Safety Issues:False
Outcome Type:Primary Outcome
Measure:drug plasma levels rosiglitazone:
Time Frame:Days 2 & 12
Safety Issues:False
Outcome Type:Primary Outcome
Measure:drug plasma levels flurbiprofen:
Time Frame:Days 3 & 13
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:adverse reactions,changes in laboratory values,changes in vital signs, & ECG changes:
Time Frame:Days 1-13
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:drug plasma levels GSK376501:
Time Frame:Days 4-13
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Safety and tolerability during dosing with GSK376501, alone and in combination with the various probe substrates.
Time Frame:Up to Day 24
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Daily predose trough GSK376501 plasma concentrations when administered alone for 7 days (Days 4-13).
Time Frame:for 7 days (Days 4-13).
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:GSK376501
Description:GSK376501 oral tablet will be available with dosing strengths of 75 milligrams administered once daily. Biconvex, It will be a round, white film-coated tablets with both plain sides and no identifying markings.
Arm Name:Subjects receiving GSK376501 + rosiglitazone
Intervention Type:Drug
Name:Midazolam
Description:Midazolam oral syrup will be available with a dose of 5 milligrams administered once daily. It will be a clear, red to purplish-red, cherry-flavored syrup.
Arm Name:Subjects receiving midazolam
Intervention Type:Drug
Name:Rosiglitazone
Description:Rosiglitazone oral tablet will be available with dosing strengths of 4 milligrams administered once daily. It will be a orange colored tablet debossed with SB on one side and 4 on the other.
Arm Name:Subjects receiving rosiglitazone
Intervention Type:Drug
Name:Flurbiprofen
Description:Rosiglitazone oral tablet will be available with dosing strengths of 50 milligrams administered once daily. It will be a blue, oval, film coated tablet.
Arm Name:Subjects receiving flurbiprofen

Study Arms

Study Arm Type:Active Comparator
Arm Name:Subjects receiving midazolam
Description:Eligible subjects will receive midazolam oral syrup with a dose of 5 milligrams on Day 1.
Study Arm Type:Active Comparator
Arm Name:Subjects receiving rosiglitazone
Description:Eligible subjects will receive rosiglitazone oral tablet with a dose of 4 milligrams on Day 2.
Study Arm Type:Active Comparator
Arm Name:Subjects receiving flurbiprofen
Description:Eligible subjects will receive flurbiprofen oral tablet with a dose of 50 milligrams on Day
Study Arm Type:Experimental
Arm Name:Subjects receiving GSK376501
Description:Eligible subjects will receive GSK376501 oral tablet with a dose of 75 milligrams from Day 4 to Day 10.
Study Arm Type:Experimental
Arm Name:Subjects receiving GSK376501+ midazolam
Description:Eligible subjects will receive GSK376501 oral tablet with a dose of 75 milligrams along with midazolam oral tablet of 5 milligrams on Day 11.
Study Arm Type:Experimental
Arm Name:Subjects receiving GSK376501 + rosiglitazone
Description:Eligible subjects will receive GSK376501 oral tablet with a dose of 75 milligrams along with rosiglitazone oarl tablet of 4 milligrams on Day 12.
Study Arm Type:Experimental
Arm Name:Subjects receiving GSK376501 + flurbiprofen
Description:Eligible subjects will receive GSK376501 oral tablet with a dose of 75 milligrams along with flurbiprofen oral tablet of 50 milligrams on Day 13.

Study Agencies

Agency Class:Industry
Agency Type:Lead Sponsor
Agency Name:GlaxoSmithKline

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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