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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01615796




Registration number
NCT01615796
Ethics application status
Date submitted
7/06/2012
Date registered
11/06/2012

Titles & IDs
Public title
Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Repeat IV Doses
Scientific title
A Two-Part Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Repeat IV Doses of GSK2140944 in Healthy Adult Subjects.
Secondary ID [1] 0 0
115198
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infections, Respiratory Tract 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Part A: GSK2140944 Drug single dose of 200mg, 600mg, 1200mg, 1800 mg, and dose to be determined
Treatment: Drugs - Part B: GSK2140944 Repeat Drug dose of 400mg, 750mg, 1000 mg, and dose to be determined

Experimental: Cohort A1 - GSK2140944 200mg single dose

Experimental: Cohort A2 - GSK2140944 600mg single dose

Experimental: Cohort A3 - GSK2140944 1200mg single dose

Experimental: Cohort A4 - GSK2140944 1800mg single dose

Experimental: Cohort A5 - GSK2140944 1800mg single dose

Experimental: Cohort A6 - GSK2140944 dose to be determined, single dose

Experimental: Cohort B1 - GSK2140944 400 mg repeat dose BID up to 7 days

Experimental: Cohort B2 - GSK2140944 750 mg repeat dose BID up to 7 days

Experimental: Cohort B3 - GSK2140944 1000 mg repeat dose BID up to 7 days

Experimental: Cohort B4 - GSK2140944 to be determined repeat dose BID up to 7 days

Experimental: Cohort B5 - GSK2140944 to be determined repeat dose TID up to 14 days

Experimental: Cohort B6 - GSK2140944 to be determined repeat dose TID up to 14 days


Treatment: Drugs: Part A: GSK2140944 Drug single dose of 200mg, 600mg, 1200mg, 1800 mg, and dose to be determined
Subjects receive a single dose of GSK2140944

Treatment: Drugs: Part B: GSK2140944 Repeat Drug dose of 400mg, 750mg, 1000 mg, and dose to be determined
Subjects will receive repeat doses of GSK2140944 BID/TID for up to 14 Days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of pharmacokinetic (PK) parameters of GSK2140944 including area under the curve following single dose administration.
Timepoint [1] 0 0
Part A up to 4 days
Primary outcome [2] 0 0
Composite of PK parameters for GSK2140944 following single dose administration
Timepoint [2] 0 0
Part A up to 4 Days
Primary outcome [3] 0 0
Composite of PK parameters for GSK2140944 including area under the curve following repeat dose administration.
Timepoint [3] 0 0
Part B Days 4, 7, 10 and 14
Primary outcome [4] 0 0
Composite of PK parameters for GSK2140944 following repeat dose administration.
Timepoint [4] 0 0
Part B Days 4, 7, 10 and 14
Primary outcome [5] 0 0
Composite of PK parameters for GSK2140944 following repeat dose administration including maximum concentration, area under the curve, accumulation ratio and clearance of parent drub.
Timepoint [5] 0 0
Part B Days 4, 7, 10 and 14
Primary outcome [6] 0 0
GSK2140944 safety parameters - adverse events
Timepoint [6] 0 0
Part A change from baseline for 15 Days. Part B change from baseline for up to 28 Days
Primary outcome [7] 0 0
GSK2140944 safety parameters - telemetry
Timepoint [7] 0 0
Part A change from baseline for 15 Days. Part B change from baseline for up to 28 Days
Primary outcome [8] 0 0
GSK2140944 safety parameters - absolute values and changes over time of hematology, clinical chemistry and urinalysis
Timepoint [8] 0 0
Part A change from baseline for 15 Days. Part B change from baseline for up to 28 Days
Primary outcome [9] 0 0
GSK2140944 safety parameters - vital signs (blood pressure, heart rate, temperature)
Timepoint [9] 0 0
Part A change from baseline for 15 Days. Part B change from baseline for up to 28 Days
Primary outcome [10] 0 0
GSK2140944 safety parameters - Electrocardiogram (ECG) measurements
Timepoint [10] 0 0
Part A change from baseline for 15 Days. Part B change from baseline for up to 28 Days
Secondary outcome [1] 0 0
A composite of pharmacokinetic parameters including dose proportionality following single and repeat doses of GSK2140944.
Timepoint [1] 0 0
44 Days in Part A, 7, 10 and 14 Days in Part B
Secondary outcome [2] 0 0
A composite of pharmacokinetic urinary parameters to estimate the urinary excretion of unchanged GSK2140944 following a therapeutically relevant dose and higher single dose in healthy volunteers.
Timepoint [2] 0 0
4 Days in Part A
Secondary outcome [3] 0 0
A composite of pharmacokinetic parameters to estimate the absolute bioavailability of the oral capsule formulation of GSK2140944 as compared to the IV formulation following single equivalent doses in healthy volunteers.
Timepoint [3] 0 0
4 Days in Part A
Secondary outcome [4] 0 0
A composite of pharmacokinetic parameters to examine the extent of accumulation and time invariance following repeat doses of GSK2140944.
Timepoint [4] 0 0
4, 7, 10 and 14 days in Part B
Secondary outcome [5] 0 0
A composite of pharmacokinetic parameters to examine achievement of steady-state following repeat doses of GSK2140944.
Timepoint [5] 0 0
7, 10 and 14 days in Part B

Eligibility
Key inclusion criteria
* AST, ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated bilirubin less than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
* 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 between 18 and 60 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. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and estradiol less than 40 pg/ml (less than 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 the protocol. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
* Body weight greater than and equal to 50 kg and BMI within the range 19 - 31 kg/m2 (inclusive).
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
* A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening.
* A screening urinalysis positive for protein or glucose (greater than "trace" findings of protein or glucose).
* A serum creatinine value between screening and Day -1 visit that is increased by more than 0.2 mg/dL (or 15.25 umol/L) changes.
* History of photosensitivity to quinolones.
* Unwillingness to commit to avoid excessive exposure to sunlight (or exposure whilst on a tanning bed) which would cause a sunburn reaction from first dose up to and including the follow-up visit.
* History of drug abuse within 6 months of the study.
* History of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
* History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units (or an average daily intake of greater than 3 units) for males or an average weekly intake of greater than 14 units (or an average daily intake greater than 2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits and 100 mL of wine.
* The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John's Wort within 14 days prior to the first dose of study medication. By exception, the volunteer may take paracetamol or acetaminophen (less than and equal to 2 grams/day) up to 48 hours prior to the first dose of study medication. However, the Investigator and GSK study team can review medication on a case by case basis to determine if its use would compromise subject safety or interfere with the study procedures or data interpretation.
* 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.
* Donation of blood in excess of 500 mL within 12 weeks prior to dosing.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* History of tendon rupture.
* Subject is mentally or legally incapacitated.
* History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
* Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
* Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate: Males - less than 40 and greater than 100 bpm; Females: less than 50 and greater than 100 bpm; PR Interval: Males and Females - less than 120 and greater than 220 msec; QRS duration: Males and Females - less than 70 and greater than 100 msec; QTcB or QTcF interval: Males and Females - greater than 450 msec; Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization); Subject has Bundle Branch Block; 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 greater than 3 seconds, non-sustained or sustained ventricular tachycardia (greater than and equal to 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.
* Screening holter monitoring shows one or more of the following: Any symptomatic arrhythmia (except isolated extra systoles); Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, SVT (greater than 10 consecutive beats)); Sinus tachycardia (or supraventricular tachycardia) greater than 150 bpm; Non-sustained or sustained ventricular tachycardia (defined as greater than and equal to 3 consecutive ventricular ectopic beats); Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher in an awake subject], WPW syndrome, other pre-excitation syndromes); Symptomatic sinus pause or sinus pause >3 seconds - unless patient is straining, vomiting, or having some other type of hypervagal response; 300 or more supraventricular ectopic beats in 24 hours; 250 or more ventricular ectopic beats in 24 hours; Ischemia, diagnosed by a sequence of EKG changes that include flat or downsloping ST-segment depression greater than 0.1 mV, with a gradual onset and offset that lasts for a minimum period of 1 minute. Each episode of ischemia must be separated by a minimum duration of at least 1 minute, during which the ST segment returns back to baseline (1x1x1 rule).
* Neutrophil count <2000 cells per microliter (a single repeat is allowed for eligibility determination).

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/02/2014
Sample size
Target
Accrual to date
Final
86
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT01615796