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

NCT01879462 | Completed Phase 1

• 1 other identifier: 116973
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hepatitis C, Chronic

Keywords

chronic hepatitis C (CHC); Hepatitis C virus (HCV); NS5B; pharmacokinetics; GSK2878175; safety; FTIH; healthy subjects

Outcome Measures

Primary Outcomes (2)

• 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).

  Screening to 7-14 days post last-dose

• 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.

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

Secondary Outcomes (7)

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

  Part 1 and Day 1for Part 2

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

  on Part 2 Day 7

• Dose proportionality of GSK2878175 PK parameters following single and repeat administration

  Pre-dose, Day1 and Day 7

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

  Pre-dose, Day1

• Estimate GSK2878175 accumulation and time invariance

  Pre-dose, Day1 and Day 7

Study Arms (6)

Cohort A

EXPERIMENTAL

Subjects 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).

Drug: GSK2878175; Drug: Placebo

Cohort B

EXPERIMENTAL

Subjects 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).

Drug: GSK2878175; Drug: Placebo

Cohort C

EXPERIMENTAL

Subjects 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).

Drug: GSK2878175; Drug: Placebo

Cohort D

EXPERIMENTAL

Subjects 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).

Drug: GSK2878175; Drug: Placebo

Cohort E

EXPERIMENTAL

Subjects 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).

Drug: GSK2878175; Drug: Placebo

Cohort F

EXPERIMENTAL

Subjects 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).

Drug: GSK2878175; Drug: Placebo

Interventions

GSK2878175 DRUG

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

Cohort A; Cohort B; Cohort C; Cohort D; Cohort E; Cohort F

Placebo DRUG

Visually matching GSK2878175

Cohort A; Cohort B; Cohort C; Cohort D; Cohort E; Cohort F

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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\]..
• 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.
• 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:
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Results for study 116973 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

GSK2878175

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2013
• First Posted: June 17, 2013
• Study Start: June 14, 2013
• Primary Completion: January 10, 2014
• Study Completion: January 10, 2014
• Last Updated: July 24, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

AU (1)