A Repeat Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Subjects

NCT ID: NCT00896558

Last Updated: 2017-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-11
• Study Completion Date: 2009-09-25

Brief Summary

This study will be the first repeat dose administration of GSK1322322 to investigate safety, tolerability, and pharmacokinetics in healthy subjects as well as elderly volunteer subjects. The study will also include a P450 probe drug (midazolam) to evaluate the effect of GSK1322322 to inhibit or induce CYP3A4 substrates.

Conditions

Infections, Bacterial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Cohort A

A single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.

Group Type: EXPERIMENTAL

GSK1322322/placebo

Intervention Type: DRUG

GSK1322322/placebo escalating doses from 500mg to 1500mg

Cohort B

Subjects will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.

Group Type: EXPERIMENTAL

GSK1322322/placebo

Intervention Type: DRUG

GSK1322322/placebo escalating doses from 500mg to 1500mg

Cohort C

Subjects in the probe cohort will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12. All subjects will receive a single dose of midazolam alone on Day -1, and co-administered with the morning dose of GSK1322322/placebo on Day 1 and Day 12.

Group Type: EXPERIMENTAL

GSK1322322/placebo

Intervention Type: DRUG

GSK1322322/placebo escalating doses from 500mg to 1500mg

GSK1322322/placebo and midazolam

Intervention Type: DRUG

GSK1322322/placebo and 5mg midazolam

Cohort D

Subjects will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.

Group Type: EXPERIMENTAL

GSK1322322/placebo

Intervention Type: DRUG

GSK1322322/placebo escalating doses from 500mg to 1500mg

Cohort E

Subjects will receive a single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12.

Group Type: EXPERIMENTAL

GSK1322322/placebo

Intervention Type: DRUG

GSK1322322/placebo escalating doses from 500mg to 1500mg

Interventions

GSK1322322/placebo

GSK1322322/placebo escalating doses from 500mg to 1500mg

Intervention Type: DRUG

GSK1322322/placebo and midazolam

GSK1322322/placebo and 5mg midazolam

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• The subject is healthy.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent (except for elderly cohort-Part B, see #8 below)..
• A female is eligible to enter and participate in this study if she is of non-childbearing potential
• Male subjects must agree to use one of the contraception methods in the protocol
• Body weight greater than or equal to 50 kg and body mass index between 18.5-29.9 kg/m2 inclusive
• Capable of giving written informed consent
• QTcB less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block on Screening ECG
• Part B/Cohort E Elderly cohort: The subject is greater than 65 years of age.

Exclusion Criteria

• The subject has a positive pre-study drug/alcohol screen.
• 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.
• History of regular alcohol consumption within 6 months of the study defined in the protocol
• 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.
• 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 human chorionic gonadotropin test at screening or prior to dosing.
• Lactating females.
• Subjects who have asthma or a history of asthma within the past 6 months.
• History of smoking or history of regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, satsuma, ugli, tangerine, and tangelo, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
• For probe cohort in Part A: any condition or symptom contraindicated for administration of midazolam including acute narrow-angle or open-angle glaucoma.

• Minimum Eligible Age: 18 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

Randwick, New South Wales, Australia

Countries

Australia

References

Naderer OJ, Dumont E, Zhu J, Kurtinecz M, Jones LS. Safety, tolerability and pharmacokinetics of repeat dosing of the antibiotic GSK1322322, a peptide deformylase inhibitor: a randomized placebo-controlled study. J Antimicrob Chemother. 2013 Aug;68(8):1901-9. doi: 10.1093/jac/dkt097. Epub 2013 Apr 3.

Reference Type: BACKGROUND

PMID: 23557930 (View on PubMed)

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: Statistical Analysis Plan

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: Dataset Specification

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

Related Links

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Other Identifiers

112668

Identifier Type: -

Identifier Source: org_study_id