Single Dose Escalation First Time in Human PK Study

Study Overview
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Brief Summary
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This is a first time in human (FTIH) study of single escalating doses of investigational study drug to investigate safety, tolerability, and pharmacokinetics in healthy subjects

Official Title
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A Double-Blind, Parallel, Randomized, Placebo-Controlled, Single Dose Escalation First Time in Human Study to Investigate the Safety, Tolerability and Pharmacokinetics of Investigational Study Drug in Healthy Subjects

Conditions
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Infections, Bacterial

Intervention / Treatment
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* Drug: 100 mg GSK investigational drug
* Drug: 200 mg GSK investigational drug
* Drug: 400 mg GSK investigational drug
* Drug: 800 mg GSK investigational drug
* Drug: 2000 mg GSK investigational drug
* Drug: 1500 mg GSK investigational drug
* Drug: 800mg fed GSK investigational drug
* Drug: 3000mg GSK investigational drug
* Drug: 4000mg GSK investigational drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male non-childbearling potential females Body weight greater than or equal to 50 kg (110 lbs) for men and greater than or equal to 45 kg (99 lbs) for women. Body mass index (BMI) between 18.5-29.9 kg/m2 inclusive. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block on Screening ECG Exclusion Criteria: The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. 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 as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). A standard unit is defined as 10g ethanol which is equivalent to 100mL wine, 250mL full strength beer, 470mL light beer, 30mL spirits The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the 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 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 [serum or urine] human chorionic gonadotropin (hCG) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>100mg | Drug: 100 mg GSK investigational drug<br> <br> * Other names: 1500 mg study drug;|
| Experimental: Cohort 2<br>200mg | Drug: 200 mg GSK investigational drug<br> <br> |
| Experimental: Cohort 3<br>400mg | Drug: 400 mg GSK investigational drug<br> <br> |
| Experimental: Cohort 4<br>800mg | Drug: 800 mg GSK investigational drug<br> <br> |
| Experimental: Cohort 5<br>1500mg | Drug: 1500 mg GSK investigational drug<br> <br> |
| Experimental: Cohort 6<br>2000mg | Drug: 2000 mg GSK investigational drug<br> <br> |
| Experimental: Cohort 7<br>800mg with food | Drug: 800mg fed GSK investigational drug<br> <br> |
| Experimental: Cohort 8<br>3000mg | Drug: 3000mg GSK investigational drug<br> <br> |
| Experimental: Cohort 9<br>4000mg | Drug: 4000mg GSK investigational drug<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety parameters, adverse events, absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram intervals, and ECG rhythm. |  | Eighteen days | 
| Pharmacokinetic parameters following single dose administration: area under the plasma concentration curve AUC 0 to inf, AUC 0 to t, AUC 0 to 24, maximum observed concentration , time to maximum observed concentration , terminal half life . |  | Two days, Three days (3000mg and 4000mg only) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0 to inf and Cmax following single dose administration for the assessment of dose proportionality |  | Two days, Three days (3000mg and 4000mg only) | 
| Amount excreted of unchanged study drug and renal clearance |  | Two days, Three days (3000mg and 4000mg only) | 
| AUC 0 to inf, AUC 0 to t, AUC 0 to 24, Cmax, tmax and tlag if deemed appropriate with and without high fat calorie meal |  | Two days, Three days (3000mg and 4000mg only) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy subjects, FTIH, single dose, food effect, healthy subjects, double-blind