Overview

Pharmacokinetic (PK) Study of GSK933776 in Healthy Volunteers

Status:
Completed
Trial end date:
2014-07-15
Target enrollment:
0
Participant gender:
All
Summary
This study is intended to enable a possible transition to intramuscular (IM) or subcutaneous (SQ) administration for subsequent studies with GSK933776 by characterizing the safety, tolerability, PK and pharmacodynamic profiles, and immunogenicity of GSK933776 following IM and SQ administration in healthy volunteers. Such alternate routes of administration may provide more options in the selection of an efficacious dose for subsequent development in patients with geographic atrophy. There will be four treatment arms in the study and participants will be assigned to 1 of 4 possible treatment arms in a 1:1:1:1 ratio. The planned number of evaluable participants for this study is 24 with 6 participants completing all critical assessments in each of the four treatment arms. The total duration of participation from screening to follow-up for Treatment Arms A, B and D (single dose of GSK933776), will be approximately 113 days and total duration for Treatment Arm C (repeat dose of GSK933776) will be approximately 134 days.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
GlaxoSmithKline
Collaborator:
Quintiles, Inc.
Treatments:
Antibodies
Criteria
Inclusion Criteria:

- Male or female subject 18 to 50 years of age at the time of signing the informed
consent

- In general good health as determined by a physician, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
monitoring. A subject with a clinical abnormality or laboratory parameters outside the
reference range for the population being studied may be included only if the
Investigator and the GSK Medical Monitor agree that the condition is unlikely to
introduce additional risk factors and will not interfere with the study procedures

- Body weight >=55 kilograms (kg) (121 pounds [lbs]) and <=85 kg (187 lbs) with a body
mass index (BMI) between 18.5 and 29 kg per meter square (inclusively) 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; 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 picogram/mL (<140
picomoles/Liter) is confirmatory.

- Male subjects must agree to use one form of acceptable contraception methods if their
partner is of childbearing potential. This criterion must be followed from the time of
the screening visit through the follow up visit (84 days after last dose of study
medication).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

Exclusion Criteria:

- Known risk history of Central nervous system (CNS) disorders: History and/or evidence
(computed tomography or magnetic resonance imaging scan performed within the past 12
months) of cerebral haemorrhage OR a known risk of cerebral haemorrhage, including
uncontrolled hypertension, cerebrovascular malformation, coagulopathy, central nervous
system (CNS) vasculitis, degenerative or inflammatory/demyelinating CNS conditions or
any other condition that the Investigator and/or the medical monitor considers as a
relevant risk factor for cerebral haemorrhage. Transient ischemic attack
(TIA)/cerebrovascular accident (CVA) in the last year, or other uncontrolled risk
factors for stroke; History of seizures (except febrile seizures in childhood) or
recent unprovoked seizure; Uncontrolled type 2 diabetes mellitus (glycated hemoglobin
>10%), active cardiovascular disease (e.g., moderate-severe angina, unstable angina,
myocardial infarction (MI) within the last 2 years, symptomatic congestive heart
failure, clinically significant arrhythmia); Current blood clotting or bleeding
disorder or conditions that predispose to these (e.g. cancer); Diagnosis of currently
active, or, in remission but chronic relapsing, systemic autoimmune disease or
condition (e.g. multiple sclerosis, lupus erythematosus etc) that the Investigator
and/or the medical monitor considers as a relevant risk factor for concomitant
administration of a therapeutic monoclonal antibody.

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- Use of prescription drugs or non-prescription drugs, including vitamins, herbal and
dietary supplements (including St John's Wort) within 7 days 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.

- A positive pre-study drug/alcohol screen. Current or recent drug or alcohol abuse or
dependence. History of regular alcohol consumption within 6 months of the study
defined as: An average weekly intake of >14 units for males or >7 units for females.
One drink is equivalent to 12 gram (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. Use of
illegal drugs.

- 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.

- Seated systolic blood pressure >140 millimeter of mercury (mmHg) or seated diastolic
blood pressure of > 90 mmHg

- QTc >450 millisecond (msec).

- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) >= 2xupper limit
of normal (ULN); alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

- Significant abnormalities on hematology screen: clinically significant anemia (i.e.
hemoglobin <11 g/deciliter [dL] for males or <10 g/dL for females), or platelet counts
below 124 Giga/L; International Normalized Ratio > 2.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- A positive test for human immunodeficiency virus antibody

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Exposure to more than four new chemical entities within 12 months prior to screening.

- Prior allergic reactions to biological products (vaccines, antibodies) or known
hypersensitivity to any of the components of the drug formulation.

- Prior participation in clinical investigations involving therapeutic monoclonal
antibodies with a similar mode of action or proteins derived from monoclonal
antibodies with any risk of cross- reactivity or any investigations of treatments or
use of any other investigational medication or device within 2 months prior to
screening or within 5 half-lives of use of such a medication prior to screening,
whichever is longer.