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

NCT01648179 | Completed Phase 1

• 1 other identifier: 116595
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Infections, Bacterial

Keywords

GSK1322322, relative bioavailability, healthy subjects, open label, food effect, weight effect

Outcome Measures

Primary Outcomes (2)

• To estimate the relative bioavailability of wet milled tablet formulations of GSK1322322 with and without food as compared to an oral mesylate salt solution following single doses in healthy subjects.

  GSK1322322 AUC(0-∞) and Cmax following wet milled tablet formulation administered with and without moderate fat/calorie meal. GSK1322322 AUC(0-∞) and Cmax following oral mesylate salt solution administration.

  72 Hours

• To estimate the effect of body weight on the pharmacokinetics of GSK1322322 formulations (IV and oral) following single dose administration to healthy subjects.

  GSK1322322 AUC(0-∞) and Cmax in each body weight group following IV or oral formulation administration to assess effect of body weight.

  72 Hours

Secondary Outcomes (2)

• To evaluate the safety and tolerability of GSK1322322 after single doses of each formulation in healthy subjects.

  14 Days

• To estimate the absolute bioavailability of the different oral formulations of GSK1322322 as compared to IV mesylate salt formulation following single doses in healthy subjects.

  72 Hours

Study Arms (4)

GSK1322322 IV formulation

EXPERIMENTAL

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

Drug: GSK1322322 (mesylate salt) Powder for Injection

GSK1322322 Wet milled Tablet (Fasted)

EXPERIMENTAL

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

Drug: GSK1322322 (freebase) tablets

GSK1322322 Oral mesylate salt solution

EXPERIMENTAL

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

Drug: GSK1322322 (mesylate salt) Powder for Oral Solution

GSK1322322 Wet milled Tablet (Fed)

EXPERIMENTAL

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

Drug: GSK1322322 (freebase) tablets FED

Interventions

GSK1322322 (mesylate salt) Powder for Injection 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 IV formulation

GSK1322322 (freebase) tablets DRUG

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

GSK1322322 Wet milled Tablet (Fasted)

GSK1322322 (mesylate salt) Powder for Oral Solution 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 Oral mesylate salt solution

GSK1322322 (freebase) tablets FED DRUG

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

GSK1322322 Wet milled Tablet (Fed)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

Related Links

• Results for study116595 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

Bacterial Infections

Interventions

GSK1322322; Powders; Injections; Tablets; Solutions

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2012
• First Posted: July 24, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: March 22, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)