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Hepatitis C, ChronicPhase 1NCT01879462

A First Time in Human Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single & Repeat Escalating Doses of GSK2878175 in Healthy Subjects

A Phase 1 study testing GSK2878175 in people with Hepatitis C, Chronic, run by GlaxoSmithKline at 1 site in Australia.

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

GSK2878175 is a site IV NS5B non-nucleoside inhibitor (NNI) being developed for the treatment of chronic HCV infection. This study represents the first administration of GSK2878175 in humans to define safety, tolerability, and pharmacokinetics (PK) following single and repeat doses of GSK2878175 in healthy subjects. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Hepatitis C, Chronic
What is being tested?
GSK2878175
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
47 participants
Where
1 siteAustralia
Study dates
14 Jun 2013to 10 Jan 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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECGs. There should be no evidence of cardiac, pulmonary, hepatic, biliary, gastrointestinal, or renal disorders, or cancer within the past 5 years (except localized or in situ cancer of the skin). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria and are reported as outside of the normal reference range for healthy volunteers may be included only if the Investigator considers the finding is unlikely to introduce additional risk to the subject and will not interfere with the study procedures.
  • Body weight >50 Kilograms(kg) (110 pounds) for men and >45kg (99pounds) women and a body mass index (BMI) between 18.5-32 kg/meter^2 inclusive will be allowed.
  • Male or female between 18 and 55 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 [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 [MlU]/milliliter [mL] and estradiol <40 picogram [pg]/mL [<147 picomoles /litre] is confirmatory]..
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  • Male subjects with female partners of child-bearing potential must agree to use contraception method. This criterion must be followed from the time of the first dose of study medication until the follow up visit.his criterion must be followed from the time of the first dose of study medication until the follow up visit (7 to 14 days post last dose).
  • Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), alkaline phosphatase, bilirubin, and creatinine less than the upper limits of normal. TSH within normal reference range. At the discretion of the principle investigator (PI) or sub-PI, these values may be repeated once.
  • White blood cell count (including neutrophil counts), hemoglobin, platelets and reticulocytes greater than the lower limits of normal. At the discretion of the PI or sub-PI, these values may be repeated once.
  • The subject's systolic blood pressure is inside the range of 90-140 millimeters of mercury (mmHg,) and diastolic blood pressure is inside the range of 45-90 mmHg. Heart rate is inside the range of 50-100 beat per minute (bpm) for female subjects or 45-100 bpm for male subjects.

Who cannot join

  • Subject is mentally or legally incapacitated.
  • Family history of prolonged QT syndrome (Torsade de Pointes) or sudden cardiac death; first-degree relative with myocardial infarction at premature age (<45 years for male relative; <55 years for female relative).
  • History of or active diagnosis of diabetes mellitus.
  • History of or active diagnosis of thyroid disease.
  • History of or active diagnosis of pulmonary disease such as asthma, emphysema, chronic obstructive pulmonary disease or interstitial lung disease.
  • History of regular alcohol consumption within 6 months of the study defined as:
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  • Australian standard: An average weekly intake of >21 units for males and >14 units for females. One unit is equivalent to 10 g of alcohol: 270mL of full strength beer (4.8%), 375mL of mid strength beer (3.5%),470mL of light beer (2.7%), 250mL pre-mix full strength spirit (5%), 100mL of wine (13.5%) and 30mL of spirit (40%).
  • Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
  • 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.
  • 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.
  • A positive Hepatitis C antibody
  • A positive pre-study Hepatitis B surface antigen.
  • A positive test for HIV antibody
  • History of regular use of tobacco- or nicotine-containing products within 3 months of the screening visit or indication of tobacco use as evidenced by a positive urine cotinine test at screening.
  • A positive pre-study drug/alcohol screen. Unwilling to refrain from use of the illicit drugs and adhere to other protocol-stated restrictions while participating in the study. Pregnant females as determined by positive urine or serum human chorionic gonadotropin (hCG) test at screening or prior to dosing.
  • QT interval corrected for heart rate (Fridericia's)> 450 milliseconds (msec); or QTc >480 msec in subjects with Bundle Branch Block.
  • 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, Supraventricular tachycardia (SVT) (>10 consecutive beats).
  • Sinus tachycardia (or supraventricular tachycardia) greater than 150 bpm
  • Non-sustained or sustained ventricular tachycardia (defined as >3 consecutive ventricular ectopic beats).
  • Any conduction abnormality (including but not specific to left or right complete bundle branch block, Atrioventicular (AV) block [2nd degree or higher in an awake subject], Wolff-Parkinson-White (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 ECG changes that include flat or down sloping ST-segment depression >0.1 millivolts (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).
  • Unable to use spirometry equipment correctly.
  • Abnormal spirometry results: Volume that has been exhaled at the end of the first second of forced expiration (FEV1 ) less than 80% of predicted value, FEV1/ Forced Vital Capacity: the determination of the vital capacity from a maximally forced expiratory effort (FVC )less than 70%
  • 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.
  • 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 5 days prior to the first dose of study medication.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • GSK Investigational Site

    Randwick, New South Wales, 2031

Other trials in Australia

About this study

Official title: A Randomized, Single-Blind, Dose Escalation, First Time in Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of GSK2878175 in Healthy Adults

GSK2878175 is a site IV NS5B non-nucleoside inhibitor (NNI) being developed for the treatment of chronic HCV infection. This study represents the first administration of GSK2878175 in humans to define safety, tolerability, and pharmacokinetics (PK) following single and repeat doses of GSK2878175 in healthy subjects.

This is a Phase 1, randomized, single-blind, placebo-controlled, dose escalation study to determine the safety, tolerability, and PK profile of GSK2878175 in single (Part 1) and repeat doses (Part 2) in healthy subjects. In addition the study will explore the effect of a moderate (30%) fat meal on single dose PK endpoints in healthy subjects.

Being tested
GSK2878175, Placebo
Keywords
chronic hepatitis C (CHC), Hepatitis C virus (HCV), NS5B, pharmacokinetics, GSK2878175, safety, FTIH, healthy subjects
Medical subject headings
Hepatitis C, Chronic, Hepatitis C

What participants receive

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

  • GSK2878175Drug

    Round tablets (5.0mg) given once daily single and repeated (to 7 days), Oral dose.

  • PlaceboDrug

    Visually matching GSK2878175

Study groups in NCT01879462
Study groupRoleWhat they receive
Cohort AExperimentalSubjects in this cohort will receive 3 treatments (either active drug or placebo for each dose level) in 3 treatment periods (one per period). Subjects will receive GSK2878175 5 mg, GSK2878175 50 mg, and GSK2878175 200 mg in treatment period 1, 2, and 3 respectively in fasted state (with 1:3 ratio of placebo to active treatment at each treatment period).
Receives: Drug: GSK2878175; Drug: Placebo
Cohort BExperimentalSubjects in this cohort will receive 3 treatments (either active drug or placebo for each dose level) in 3 treatment periods (one per period). Subjects will receive GSK2878175 15 mg in fasted state, GSK2878175 100 mg in fasted state, and GSK2878175 100 mg in fed state in treatment period 1, 2, and 3 respectively (with 1:3 ratio of placebo to active treatment at each treatment period).
Receives: Drug: GSK2878175; Drug: Placebo
Cohort CExperimentalSubjects in this cohort will receive GSK2878175 15 mg single dose or placebo for 7 days in fasted state (with 1:4 ratio of placebo to active treatment).
Receives: Drug: GSK2878175; Drug: Placebo
Cohort DExperimentalSubjects in this cohort will receive placebo and GSK2878175 50 mg single dose or placebo for 7 days in fasted state, (with 1:4 ratio of placebo to active treatment).
Receives: Drug: GSK2878175; Drug: Placebo
Cohort EExperimentalSubjects in this cohort will receive placebo and GSK2878175 100 mg single dose or placebo for 7 days in fasted state, (with 1:4 ratio of placebo to active treatment).
Receives: Drug: GSK2878175; Drug: Placebo
Cohort FExperimentalSubjects in this cohort will receive placebo and GSK2878175 200 mg single dose or placebo for 7 days in fasted state, (with 1:4 ratio of placebo to active treatment).
Receives: Drug: GSK2878175; Drug: Placebo

What is being measured

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

  1. Safety as assessed by the collection of adverse events (AEs).

    AEs will be collected from the start of Study Treatment and until 7-14 days post last-dose (at follow up).

    Measured: Screening to 7-14 days post last-dose

  2. Safety as assessed by hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram (ECG) intervals, ECG rhythm telemetry, pulmonary function tests, respiratory rate and lung auscultation.

    Absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs (blood pressure [BP], FSH/Estradiol (Women), Urine β-hCG (Women) temperature, and heart rate), 12 LED ECG, and Holter monitoring, ECG intervals, ECG rhythm, and telemetry will be measured. Telemetry is the continuous monitoring of a subject's heart rate and rhythm from a remote location. Pulmonary function testing includes a group of tests that measure how well the lung is functioning.

    Measured: Pre-dose to 7-14 days post last-dose

Secondary outcomes (7)

  1. Composite of pharmacokinetics (PK) parameters following single dose administration of GSK2878175.

    PK parameters 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 last time of quantifiable concentration (AUC [0-t]), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), observed concentration at 24hour post-dose (C24), lag time before observation of drug concentrations in sampled matrix (tlag), terminal half-life (t1/2), apparent oral clearance (CL/F).

    Measured: Part 1 and Day 1for Part 2

  2. Composite of PK parameters following repeat dose administration of GSK2878175.

    PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, and Ctau (Pre-dose trough concentration at the end of the dosing interval),tmax, tlag, t1/2, CL/F

    Measured: on Part 2 Day 7

  3. Dose proportionality of GSK2878175 PK parameters following single and repeat administration

    GSK2878175 PK parameters: AUC (0-infinity), AUC (0-t), Cmax, and Ctau (Pre-dose trough concentration at the end of the dosing interval),tmax, tlag, t1/2

    Measured: Pre-dose, Day1 and Day 7

  4. The effect of a moderate fat/caloric meal on the relative bioavailability of a given single dose of GSK2878175

    GSK2878175 PK parameters: AUC (0-infinity), AUC (0-t), Cmax, and Ctau (Pre-dose trough concentration at the end of the dosing interval), tmax, tlag, t1/2, with and without moderate fat/calorie meal (Part 1).

    Measured: Pre-dose, Day1

  5. Estimate GSK2878175 accumulation and time invariance

    GSK2878175 AUC(0 t), Cmax, and Ctau on the last day of dosing compared to AUC(0-24), Cmax, and C24 on Day 1 to estimate accumulation ratio (R) and GSK2878175 AUC(0 t) on the last day of dosing compared to AUC(0 infinity) on Day 1 to evaluate time invariance (Part 2)

    Measured: Pre-dose, Day1 and Day 7

  6. To assess attainment of steady state following repeat administration

    Pre-dose concentrations on Day 3 through 7 and Ctau on Day 7 to assess the achievement of steady state of GSK2878175 following repeat administration (Part 2).

    Measured: Pre-dose, Day 1 and Day 7

  7. To describe exposure-response relationships for various safety parameters, if appropriate.

    Correlation between PK parameters and various safety parameters, if appropriate

    Measured: Pre-dose, Day1 and Day 7

Timeline

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

  1. First posted17 Jun 2013 (estimated)
  2. Study start14 Jun 2013
  3. Primary completion10 Jan 2014
  4. Study completion10 Jan 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
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01879462
Sponsor's protocol ID
116973
Status last verified
Jul 2018
First submitted
13 Jun 2013
Last updated
24 Jul 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2878175 in people with Hepatitis C, Chronic, run by GlaxoSmithKline at 1 site in Australia.

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 10 inclusion and 32 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 24 Jul 2018. 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 Australia. 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?

Safety as assessed by the collection of adverse events (AEs). (time frame: Screening to 7-14 days post last-dose). The study lists 2 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 NCT01879462.

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 24 Jul 2018.

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