Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Escalating Doses of GSK1325756 Solution for Infusion, and Absolute Bioavailability Relative of an Oral Dose, in Healthy Adult Subjects

NCT ID: NCT02169583

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-12
• Study Completion Date: 2014-08-28

Brief Summary

This will be the first time GSK1325756 Solution for Infusion formulation that has been administered to humans. Prior studies have been performed with oral GSK1325756. The primary objectives of this study are to obtain information on the safety, tolerability, and pharmacokinetics (PK) of single and twice daily intravenous (IV) administration of GSK1325756 in healthy subjects. In Part A, single, escalating doses will be given in the same cohort of subjects after a seven day washout. In addition, the study will evaluate the absolute bioavailability of a single dose of the current oral tablet formulation as compared to the IV formulation in Part A. In Part B, twice daily (BID) intravenous dose administration will be given for 5 days (9 total doses) in two separate cohorts of subjects. Data from this study will provide understanding of the safety, tolerability, and PK of intravenously administered GSK1325756 twice daily to guide dose selection in future clinical studies in patients with viral respiratory tract infections

Conditions

Infections, Respiratory Tract

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A (Cohort 1)

Approximately 8 subjects (6 Active, 2 Placebo) will be randomized to receive single escalating IV doses i.e.10 milligrams (mg), 25 mg and 100 mg, plus one oral 100 mg dose (on the last occasion) of GSK1325756 or matching placebo, with a 7-days washout between doses. Dose escalations will be based on review of PK and safety data from preceding dose level. The projected doses for each group are subject to modification based upon PK and safety data from preceding cohorts. Pharmacokinetic parameters will be reviewed from at least 4 active subjects from preceding dose before dose escalating to the next dose level. The maximum dose administered will be 100 mg. Additional subjects/Cohorts may be enrolled.

Group Type: EXPERIMENTAL

GSK1325756 Solution

Intervention Type: DRUG

Solution containing 2 mg/mL GSK1325756 in sterile water for injection, to be administered intravenously.

GSK1325756 Solution Matching Placebo

Intervention Type: DRUG

Solution containing sterile water for injection matching GSK1325756 solution, to be administered intravenously.

GSK1325756 Tablet

Intervention Type: DRUG

A white film coated tablet containing 50 mg GSK1325756 to be administered orally.

GSK1325756 Tablet Matching Placebo

Intervention Type: DRUG

A white film coated tablet matching GSK1325756 tablet, to be administered orally.

Part B (Cohorts 2 and 3)

Approximately 8 subjects (6 Active, 2 Placebo) per cohort will be randomized to receive escalating repeated IV doses of GSK1325756 or matching placebo (Cohort 2: 25 mg, Cohort 3: 50 mg) for 5 days. Repeated (BID) doses of GSK1325756 will begin the morning of Day 1 and continue through the morning of Day 5 (9 total doses). Dose escalations will be based on review of PK and safety data from preceding dose level. The projected doses for each group are subject to modification based upon PK and safety data from preceding cohorts. Pharmacokinetic parameters will be reviewed from at least 4 active subjects from preceding dose before dose escalating to the next dose level. The maximum dose administered will be 50 mg BID. Additional subjects/Cohorts may be enrolled.

Group Type: EXPERIMENTAL

GSK1325756 Solution

Intervention Type: DRUG

Solution containing 2 mg/mL GSK1325756 in sterile water for injection, to be administered intravenously.

GSK1325756 Solution Matching Placebo

Intervention Type: DRUG

Solution containing sterile water for injection matching GSK1325756 solution, to be administered intravenously.

Interventions

GSK1325756 Solution

Solution containing 2 mg/mL GSK1325756 in sterile water for injection, to be administered intravenously.

Intervention Type: DRUG

GSK1325756 Solution Matching Placebo

Solution containing sterile water for injection matching GSK1325756 solution, to be administered intravenously.

Intervention Type: DRUG

GSK1325756 Tablet

A white film coated tablet containing 50 mg GSK1325756 to be administered orally.

Intervention Type: DRUG

GSK1325756 Tablet Matching Placebo

A white film coated tablet matching GSK1325756 tablet, to be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Body weight >=60 kilograms (kg) for men and >=45 kg for women; and Body Mass Index (BMI) within the range 19 to 32 kg/square meter (m^2) (inclusive).
• 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 [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-international unit (MIU)/milliliter (mL) and estradiol <40 picograms (pg)/mL (<147 picomoles [pmol]/liter [L]) is confirmatory].
• Male subjects with female partners of child-bearing potential must agree to use one of the acceptable contraception methods. This criterion must be followed from the time of the first dose of study medication until 90 days following the last dose.
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Based on a single ECG obtained over a brief recording period: corrected QT interval (QTc) <450 milliseconds (msec); or QTc <480 msec in subjects with Bundle Branch Block.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• 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 grams (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.
• 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 GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
• Part A only: Subjects currently or likely to take antacids (H2 receptor antagonists, proton pump inhibitors [PPI] blockers, etc.) at any point during the study.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Urinary cotinine levels indicative of smoking history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• A positive pre-study drug/alcohol screen.
• A positive test for human immunodeficiency virus (HIV) antibody.
• Pregnant females as determined by positive (serum or urine) human chorionic gonadotropin (hCG) test at screening or prior to dosing.
• Subjects with a peripheral blood neutrophil count at the screening visit <2 x 10^9/L.
• Subjects with a history of renal disease or subjects with an abnormal urinalysis (confirmed on repeat) suggesting the possibility of renal disease (e.g. proteinuria).
• Subjects with a serum creatinine at the screening visit >1 x ULN.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 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

Overland Park, Kansas, United States

Countries

United States

Study Documents

Document Type: Dataset Specification

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: Annotated Case Report Form

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

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: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

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Other Identifiers

201022

Identifier Type: -

Identifier Source: org_study_id