A Phase I Rheumatoid Arthritis Study in Healthy Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00539760
• Date of registration: 04/10/2007
• Primary sponsor: GlaxoSmithKline
• Public title: A Phase I Rheumatoid Arthritis Study in Healthy Volunteers
• Scientific title: A Phase I, Randomized, Observer- and Subject-Blind, Placebo-Controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK1827771 in Healthy Volunteers
• Date of first enrolment: September 2007
• Target sample size: 45
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00539760
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Healthy adult men or women as determined by a responsible physician, based on a
medical evaluation including history, physical examination, laboratory tests and
cardiac assessment.

- Female subjects of non-childbearing potential.

- Male subjects must agree to abstain from or agree to use adequate contraception, in
addition to having their female partner use another form of contraception. This
criterion must be followed from the time of the first dose of study medication until
PK levels are determined to be below the LLQ.

- Men or women who are between 18 and 55 years of age, inclusive.

- BMI within the range of 18-35 kg/m2 inclusive.

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

Exclusion Criteria:

- The subject has a positive pre-study urine drug/urine alcohol screen. A minimum list
of drugs that will be screened for includes amphetamines, barbiturates, cocaine,
opiates, cannabinoids and benzodiazepines.

- A history of regular alcohol consumption averaging >7 drinks/week for females or >14
drinks/week for males. One drink is equivalent to (12 g alcohol) = 5 ounces (150 mL)
of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled
spirits

- The subject is unwilling to abstain from alcohol consumption from 48 hr prior to
dosing until discharge from the clinic, and for 48 hr prior to all other out-patient
clinic visits.

- Smoked or used tobacco or nicotine-containing products within the previous 6 months
prior to the first dose of current study medication.

- The subject has participated in a clinical trial and has received a drug or a new
chemical entity within 30 days or 5 half-lives, or twice the duration of the
biological effect of any drug (whichever is longer) prior to the first dose of
current study medication.

- Previous exposure to or treatment with PEGylated molecules.

- Use of anti-Tumor Necrosis Factor (anti-TNF) drugs within 60 days prior to dosing.

- Use of prescription 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.

- History of sensitivity to any of the study medications, or components thereof, or a
history of drug or other allergy (including antibiotics) which, in the opinion of the
investigator and/or GSK Medical Monitor, contraindicates the subject's participation.

- Positive pregnancy test at Screening or on Day -1 (females only).

- Any clinically significant abnormality identified on the screening medical assessment
or examination, or ECG.

- Any WBC or neutrophil count outside the normal range at screening or on Day -1.

- History of significant cardiac, pulmonary, metabolic, renal, hepatic, or
gastrointestinal conditions that in the opinion of the investigator and/or GSK
Medical Monitor, places the subject at an unacceptable risk as participant in this
trial.

- History of any autoimmune or current inflammatory conditions including rheumatoid
arthritis or any other joint disease.

- History of malignancy, except for surgically cured basal cell carcinoma or cured
cervical carcinoma (> 2 yrs prior to dosing).

- Currently has asthma or history of COPD.

- Current evidence of ongoing or acute infection.

- The subject has a history of repeated, chronic or opportunistic infections which, in
the opinion of the investigator and/or GSK Medical Monitor, places the subject at an
unacceptable risk as a participant in this trial.

- History of Mycobacterium tuberculosis or any other previous Mycobacterium infection.

- A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or
HIV antibody testing result.

- History of a severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency

- History of elevated blood pressure or blood pressure >140/90 mmHg at screening.

- Corrected QT interval (QTc) > 450 msec.

- Where participation in study would result in donation of blood in excess of 500 mL
within 56 days of starting the study.

- Subject whose calculated creatinine clearance is less than 80 mL/min

- Liver function tests above the upper limit of normal at screening (alkaline
transaminase (ALT), aspartate transaminase (AST) or bilirubin).

- Chronic liver or biliary disease, history of Gilbert's syndrome in a previous
clinical study or at screening.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: GSK1827771

Primary Outcome(s)

Safety and tolerability of GSK182771 at ascending doses monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary) [Time Frame: monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary)]

Secondary Outcome(s)

anti-GSK1827771, anti-PEG and anti-dAb antibodies.

Pharmacokinetics, pharmacodynamics, immunogenicity of GSK1827771. monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary) [Time Frame: monitoring will take place during the period the subjects are in-house (7 days) and when they come for the following visits (day 14, day 21, day 28 and follow-up if necessary)]

Plasma concentrations of GSK1827771 to derive pharmacokinetic parameters

response of whole blood ex vivo stimulation as a measure of the in vivo pharmacodynamic activity of GSK1827771

various exploratory biomarker levels

Secondary ID(s)

110394

Source(s) of Monetary Support

Please refer to primary and secondary sponsors