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Infections, Respiratory TractPhase 1NCT02169583

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

A Phase 1 study testing GSK1325756 Solution and GSK1325756 Tablet in people with Infections, Respiratory Tract, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Infections, Respiratory Tract
What is being tested?
GSK1325756 Solution and GSK1325756 Tablet
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteUnited States
Study dates
12 Jun 2014to 28 Aug 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Males/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including (medical history, physical examination, laboratory tests and ECG). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Overland Park, Kansas, 66211

Other trials in United States

About this study

Official title: A Two Part, Phase I, Randomized, Placebo Controlled, Double Blind 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 Protocol 201022

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

Being tested
GSK1325756 Solution, GSK1325756 Solution Matching Placebo, GSK1325756 Tablet, GSK1325756 Tablet Matching Placebo
Keywords
GSK1325756, Safety, Bioavailability, Pharmacokinetics
Medical subject headings
Respiratory Tract Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1325756 SolutionDrug

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

  • GSK1325756 Solution Matching PlaceboDrug

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

  • GSK1325756 TabletDrug

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

  • GSK1325756 Tablet Matching PlaceboDrug

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

Study groups in NCT02169583
Study groupRoleWhat they receive
Part A (Cohort 1)ExperimentalApproximately 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.
Receives: Drug: GSK1325756 Solution; Drug: GSK1325756 Solution Matching Placebo; Drug: GSK1325756 Tablet; Drug: GSK1325756 Tablet Matching Placebo
Part B (Cohorts 2 and 3)ExperimentalApproximately 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.
Receives: Drug: GSK1325756 Solution; Drug: GSK1325756 Solution Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of subjects with adverse events (AEs)

    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product

    Measured: Part A and Part B: from Day -1 until 7 to 10 days post-last dose

  2. Changes over time in clinical laboratory evaluations from pre-dose values

    Clinical laboratory assessments will include hematology, clinical chemistry, urinalysis parameters

    Measured: Part A and Part B: from Day -1 until 7 to 10 days post-last dose

  3. Changes over time in vital signs from pre-dose values

    Vital sign measurements will include systolic and diastolic blood pressure and pulse rate

    Measured: Part A and Part B: from Day -1 until 7 to 10 days post-last dose

  4. Changes over time in electrocardiogram (ECG) parameters from pre-dose values

    12-lead ECGs will be obtained at each timepoint

    Measured: Part A and Part B: from Day -1 until 7 to 10 days post-last dose

  5. GSK1325756 PK parameters following single dose administration in Part A and on Day 1 of Part B

    PK parameters will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)], area under the concentration-time curve from time zero (pre-dose) to time t [AUC(0-t)], area under the concentration-time curve from time zero (pre-dose) to 24 hours [AUC(0-24)], maximum observed concentration (Cmax), time to maximum observed concentration (tmax), observed concentration at 24 hours post-dose (C24), terminal half-life (t1/2), time of last measurable concentration (tlast), clearance (CL) and volume of distribution (Vz)

    Measured: Part A: Pre-dose, 0.5 hour (hr), 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose in each treatment period.

  6. GSK1325756 PK parameters following repeat dose administration (Part B, Day 5)

    PK parameters will include area under the concentration-time curve from time zero (pre-dose) to the end of the dosing interval [AUC(0-tau)], concentration at the end of the dosing interval (Ctau), Cmax, tmax, t1/2, Volume of distribution at steady-state (Vdss), and oral clearance (CL/F)

    Measured: Part B: Day 5 at pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and 24 hrs post-dose

Secondary outcomes (6)

  1. GSK1325756 PK parameters following single and repeat IV dose administration to assess dose proportionality

    PK parameters will include AUC(0-infinity), AUC(0-t), Cmax, and C24 following single IV dose administration (Part A) and AUC(0-tau), Ctau, and Cmax following repeated IV dose administration (Part B)

    Measured: Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose. Part B: Day 1 and Day 5: pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and (Day 5 only) 24 hrs post-dose. Day 2-4: pre-dose (each dose)

  2. GSK1325756 PK parameters following single IV and oral dose administration of a given dose of GSK1325756 (Part A) to determine the absolute bioavailability

    PK parameters will include AUC(0-infinity), AUC(0-t), Cmax and tmax

    Measured: Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose

  3. GSK1325756 accumulation ratio

    GSK1325756 AUC(0-tau), Cmax, and Ctau on the last day of dosing will be compared to area under the concentration-time curve from time zero (pre-dose) to 12 hours [AUC(0-12)], Cmax, and observed concentration at 12 hours post-dose (C12) on Day 1 to estimate accumulation ratio

    Measured: Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose Part B: Day 1 and Day 5: pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and (Day 5 only) 24 hrs post-dose. Day 2-4: pre-dose (each dose)

  4. GSK1325756 time invariance

    GSK1325756 AUC(0-tau) on the last day of dosing in Part B, will be compared to AUC(0-infinity) on Day 1 of Part A to evaluate time invariance

    Measured: Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose Part B: Day 1 and Day 5: pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and (Day 5 only) 24 hrs post-dose. Day 2-4: pre-dose (each dose)

  5. GSK1325756 Pre-dose concentrations (C12/Ctau) on Day 2 through 4

    GSK1325756 Pre-dose concentrations on Day 2 through 4 will be used to assess the achievement of steady state of GSK1325756 following repeat administration (Part B)

    Measured: Part B: Day 2 to Day 4 (pre-dose; each dose)

  6. Correlation between PK parameters and various safety parameters, if appropriate

    Measured: Part A and Part B: from Day -1 until 7 to 10 days post-last dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2014 (estimated)
  2. Study start12 Jun 2014
  3. Primary completion28 Aug 2014
  4. Study completion28 Aug 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02169583
Sponsor's protocol ID
201022
Status last verified
May 2017
First submitted
5 Jun 2014
Last updated
15 May 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1325756 Solution and GSK1325756 Tablet in people with Infections, Respiratory Tract, run by GlaxoSmithKline at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of subjects with adverse events (AEs) (time frame: Part A and Part B: from Day -1 until 7 to 10 days post-last dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02169583.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.

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