A Study to Assess the Relative Bioavailability of Three Formulations and Food Effect on GSK1322322 in Healthy Subjects

NCT ID: NCT01648179

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2012-05-31

Brief Summary

This study is an open-label, randomized, single dose, four period, balanced crossover study to assess in eligible healthy male or female subjects.

Detailed Description

This study is an open-label, randomized, single dose, four period, balanced crossover study to assess in eligible healthy male or female subjects:

• The relative bioavailability of the wet milled GSK1322322 tablet formulation with and without food compared to an oral mesylate salt solution.
• The effect of body weight on the pharmacokinetics of GSK1322322 when given either orally or IV.
• The absolute bioavailability of the wet milled tablet and the oral mesylate salt solution compared to the IV formulation.

Conditions

Infections, Bacterial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GSK1322322 IV formulation

Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via IV formulation

Group Type: EXPERIMENTAL

GSK1322322 (mesylate salt) Powder for Injection

Intervention Type: DRUG

1500 mg (mesylate salt) as free base, dissolved in sterile water for injection to a concentration of 100 mg/mL free base equivalent and sterilized via filtration. 15 mL of solution, equivalent to 1500 mg GSK 1322322, is the diluted into 0.9% Sodium Chloride Injection prior to infusion

GSK1322322 Wet milled Tablet (Fasted)

Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via Wet milled Tablet (Fasted)

Group Type: EXPERIMENTAL

GSK1322322 (freebase) tablets

Intervention Type: DRUG

500 mg tablets for a 1500 mg total single dose (3 tablets). Taken with 240 mL of water

GSK1322322 Oral mesylate salt solution

Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via Oral mesylate salt solution

Group Type: EXPERIMENTAL

GSK1322322 (mesylate salt) Powder for Oral Solution

Intervention Type: DRUG

1500 mg as a free base, dissolved in purified water to a concentration of 100 mg/mL free base equivalent. 15 mL of solution, equivalent to1500 mg GSK1322322 is administered orally with 225 mL of water

GSK1322322 Wet milled Tablet (Fed)

Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via Wet milled Tablet (Fed)

Group Type: EXPERIMENTAL

GSK1322322 (freebase) tablets FED

Intervention Type: DRUG

Drug 500 mg tablets for a 1500 mg total single dose (3 tablets) (FED moderate fat meal) Taken with 240 mL of water

Interventions

GSK1322322 (mesylate salt) Powder for Injection

1500 mg (mesylate salt) as free base, dissolved in sterile water for injection to a concentration of 100 mg/mL free base equivalent and sterilized via filtration. 15 mL of solution, equivalent to 1500 mg GSK 1322322, is the diluted into 0.9% Sodium Chloride Injection prior to infusion

Intervention Type: DRUG

GSK1322322 (freebase) tablets

500 mg tablets for a 1500 mg total single dose (3 tablets). Taken with 240 mL of water

Intervention Type: DRUG

GSK1322322 (mesylate salt) Powder for Oral Solution

1500 mg as a free base, dissolved in purified water to a concentration of 100 mg/mL free base equivalent. 15 mL of solution, equivalent to1500 mg GSK1322322 is administered orally with 225 mL of water

Intervention Type: DRUG

GSK1322322 (freebase) tablets FED

Drug 500 mg tablets for a 1500 mg total single dose (3 tablets) (FED moderate fat meal) Taken with 240 mL of water

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• QTcB < 450 msec; or QTcB < 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.
• Male or female (of non childbearing potential) 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 hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample withsimultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<147 pmol/L) is confirmatory].
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until the final follow up visit.
• Body weight ≥ 40 kg (Refer to Table 3 for weight stratification details).
• 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
• 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 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 >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.
• 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 due to potential drug interaction.
• 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.10. 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.
• 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 pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication.

• Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization).
• Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses> 3 seconds, non-sustained or sustained ventricular tachycardia (≥3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• 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

Minneapolis, Minnesota, United States

Countries

United States

Study Documents

Document Type: Annotated Case Report Form

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

View Document

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: Individual Participant Data Set

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: Dataset Specification

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

Related Links

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Other Identifiers

116595

Identifier Type: -

Identifier Source: org_study_id