Single Dose Escalation Trial to Evaluate the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of GSK3050002

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Colitis, Ulcerative

Treatments: Drug: Placebo; Drug: GSK3050002

Study type: Interventional

Funder types: Industry

Identifiers

NCT01984047

200784

Details and patient eligibility

About

The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Subjects will be admitted to the clinical unit the evening prior to dosing when each subject will receive a single intravenous dose of GSK3050002 or placebo, then remain in house under supervision until discharged on Day 3. Subjects will then return for 7 outpatient visits scheduled over the following 81 days. Finally, the follow-up visit will be 7-14 days following the last visit.

Enrollment: 49 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male 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 12- lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria may be included only if the Investigator in consultation with the GSK Medical Monitor [if required] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Body mass index (BMI) within the range 18 - 29 kilogram per meter square [kg/m^2] (inclusive).
• Male subjects with female partners of child-bearing potential must agree to use one of the listed contraception methods. This criterion must be followed for 1 month prior to the first dose of study medication for 15 weeks post dose.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Suitable for cannulation and with adequate venous access.
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5xUpper limit of Normal [ULN] (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Based on a single ECG QTcF < 450 milliseconds (msec).

Exclusion criteria

• Criteria Based Upon Medical Histories
• 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 >21 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of 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 GSK Medical Monitor, contraindicates their participation.
• History of severe drug allergies including type 1 hypersensitivity reaction to parental administration of contrast agents, human or murine proteins or monoclonal antibodies.
• Subject has acne which requires prescription treatment
• Criteria Based Upon Diagnostic Assessments
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A positive pre-study drug/alcohol screen.
• A positive test for Human immunodeficiency virus (HIV) antibody.
• Subject is a heavy smoker as defined by a positive smoking breath test of >10 parts per million (ppm) carbon monoxide (CO).
• Other Criteria
• Evidence of current or at risk of developing bacterial, fungal, or viral infection at screening or within 7 days before dosing.
• 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).
• Subject is unable to refrain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
• Subject is unable to abstain from travelling to area which carry a high risk of infection for the duration of the study.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Subject is unable to abstain from being vaccinated or immunized for 4 weeks prior to dosing and for 19 weeks after the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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49 participants in 6 patient groups

GSK3050002 0.1 mg

Experimental group

Description:

Six subjects in this cohort will receive a single dose of GSK3050002 0.1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects (i.e. 1 subject will be dosed with GSK3050002 and 1 with placebo before the remainder of the cohort is dosed) will be used in the cohort.

Treatment:

Drug: GSK3050002

Drug: Placebo

GSK3050002 0.5 mg

Experimental group

Description:

Six subjects in this cohort will receive a single dose of GSK3050002 0.5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Treatment:

Drug: GSK3050002

Drug: Placebo

GSK3050002 1 mg

Experimental group

Description:

Six subjects in this cohort will receive a single dose of GSK3050002 1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort

Treatment:

Drug: GSK3050002

Drug: Placebo

GSK3050002 5 mg

Experimental group

Description:

Six subjects in this cohort will receive a single dose of GSK3050002 5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Treatment:

Drug: GSK3050002

Drug: Placebo

GSK3050002 10 mg

Experimental group

Description:

Six subjects in this cohort will receive a single dose of GSK3050002 10 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Treatment:

Drug: GSK3050002

Drug: Placebo

GSK3050002 20 mg

Experimental group

Description:

Six subjects in this cohort will receive a single dose of GSK3050002 20 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort.

Treatment:

Drug: GSK3050002

Drug: Placebo