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

Infections, Bacterial Clinical Trial

Official title:

A Double-Blind, Parallel, Randomized, Placebo-Controlled, Repeat Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00896558
• Other study ID #: 112668
• Status: Completed
• Phase: Phase 1
• First received: May 7, 2009
• Last updated: June 21, 2017
• Start date: May 11, 2009
• Est. completion date: September 25, 2009

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 25, 2009
• Est. primary completion date: September 25, 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bacterial Infections
• Infections, Bacterial

Intervention

Drug:
• GSK1322322/placebo
GSK1322322/placebo escalating doses from 500mg to 1500mg
• GSK1322322/placebo and midazolam
GSK1322322/placebo and 5mg midazolam

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Randwick	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Australia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GSK1322322 safety parameters, adverse events , absolute values and changes over time of clinical lab testing, vital signs, electrocardiogram		6 weeks
Primary	GSK1322322 pharmacokinetic parameters following single dose administration on Day 1 and following repeat administration where applicable on Day 7 and Day 12.		15 days
Secondary	PK for midazolam with and without GSK1322322		15 days
Secondary	Blood PK for GSK1322322		15 days
Secondary	Urine PK for GSK1322322		15 days
Secondary	GSK1322322 Age Effect on PK Blood and Urine		15 days

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 112668 can be found on the GSK Clinical Study Register.