Study of Danirixin in Japanese Healthy Elderly Male Subjects

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: Placebo; Drug: GSK1325756H

Study type: Interventional

Funder types: Industry

Identifiers

NCT03136380

206817

Details and patient eligibility

About

Danirixin is a selective chemokine receptor antagonist being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the study is to assess the safety, tolerability and pharmacokinetics (PK) in healthy Japanese subjects over the age of 65 years (inclusive). The study will be conducted in two parts: Part 1 will be a double blind, placebo-controlled, 3-period crossover, ascending single oral dose administration of GSK1325756H (Hydrobromide Salt Tablet Formulations of Danirixin) 10, 50 and 100 milligram (mg) in the fed condition. Part 2 will be an open label, 2-period crossover, single oral dose of GSK1325756H 50 mg in fed and fasted state. This study will provide an understanding of PK of hydrobromide salt of GSK1325756 in population of healthy elderly subjects and also contribute to the selection of appropriate dosing for Phase IIa study in Japan.

Enrollment: 34 patients

Sex: Male

Ages: 65+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Participant must be over 65 years of age inclusive, at the time of signing the informed consent.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Participants whose peripheral blood neutrophil counts and hematocrit values are within normal range at screening visit.
• Body weight >=50 kilogram (Kg) and body mass index (BMI) within the range 18.5-24.9 kg/square meter (m^2) (inclusive).
• Japanese Male: A male participant must agree to use contraception during the treatment period and until follow up visit.
• Capable of giving signed informed consent.

Exclusion Criteria

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Abnormal blood pressure as determined by the investigator.
• Alanine Aminotransferase (ALT)>1.5x upper limit of normal (ULN).
• Bilirubin>1.5xULN (isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF)> 450 millisecond (msec).
• Past or intended use of over-the-counter or prescription medication including herbal medications and proton pump inhibitor (PPI) within 14 days prior to dosing.
• History of donation of blood or blood products >=400 milliliter (mL) within 3 months or >=200 mL within 1 month prior to screening.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrolment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research.
• The subject with positive Serological test for syphilis (Rapid Plasma Reagin [RPR] and Treponema pallidum hemagglutination test [TPHA]), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.
• Positive pre-study drug screen.
• Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of > 14 units for males. One unit is equivalent to 350 mL of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.
• Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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34 participants in 5 patient groups

Part 1: Group A

Experimental group

Description:

Subjects will receive GSK1325756H 10 mg in P-1, GSK1325756H 50 mg in P-2 and placebo in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period.

Treatment:

Drug: Placebo

Drug: GSK1325756H

Part 1: Group B

Experimental group

Description:

Subjects will receive GSK1325756H 10 mg in P-1, placebo in P-2 and GSK1325756H 100 mg in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period.

Treatment:

Drug: Placebo

Drug: GSK1325756H

Part 1: Group C

Experimental group

Description:

Subjects will receive placebo in P-1, GSK1325756H 50 mg in P-2 and GSK1325756H 100 mg in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period.

Treatment:

Drug: Placebo

Drug: GSK1325756H

Part 2: Group D

Experimental group

Description:

Subjects will receive GSK1325756H 50 mg after a low fat meal and fasted state respectively. There will be a washout period of at least 7 days between each treatment period.

Treatment:

Drug: GSK1325756H

Part 2: Group E

Experimental group

Description:

Subjects will receive GSK1325756H 50 mg after a fasted state and a low fat meal respectively. There will be a washout period of at least 7 days between each treatment period.

Treatment:

Drug: GSK1325756H