Phase I Study of GSK2982772 in Japanese Healthy Male Participants

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Autoimmune Diseases

Treatments: Drug: Placebo; Drug: GSK2982772

Study type: Interventional

Funder types: Industry

Identifiers

NCT03590613

205037

Details and patient eligibility

About

The study plans to enroll approximately 12 subjects. The main objective of the study is to assess the safety, tolerability and pharmacokinetics (PK) of the three times a day (TID), dosing of GSK2982772, in Japanese healthy male subjects. The study will comprise of four study periods each at least 7 days in duration with subjects in-house for 4 nights (through 72 hrs after the first dose). During each treatment period (TP), subjects will be admitted to the unit the day before dosing and will be discharged after completion of the 72 hours post-dose assessments. There will be a washout of atleast 7-days between the TP doses for each individual, post which there will be 7-days follow-up. The dose range proposed in this study is based on a low starting dose, which will be escalated to the highest dose that is intended for the Phase 2b dose range study. The decision to proceed to the next dose-level, of GSK2982772 within the study will be made by principal investigator and GSK Medical Monitor per each dosing periods. The study duration is approximately 22 weeks.

Enrollment: 13 patients

Sex: Male

Ages: 20 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Subject must be 20 to 64 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the Investigators based on a medical evaluation including medical history, physical examination, neurological 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 Investigators in consultation with the GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 18.5-24.9 kg/meter square (inclusive).
• Japanese male subjects must agree to use contraception as detailed in protocol during the treatment period and until follow up visit.
• Capable of giving informed consent as described in the protocol.

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 investigators.
• Symptomatic herpes zoster within 3 months prior to screening.
• Evidence of active or latent Tuberculosis (TB) as documented by medical history and examination, chest X-rays (anterior and lateral), and TB testing (T Spot. TB)
• ALT >1.5 times upper limit of normal (ULN).
• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN 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).
• History of active infections within 14 days of first receiving study medication.
• Corrected Q-T interval (QTc) obtained using the Fridericia's formula (QTcF) > 450 millisecond.
• History or diagnosis of obstructive sleep apnoea, or a significant respiratory disorder. Childhood asthma that was fully resolved is permitted.
• History of active Suicidal Ideation Behavior within the past 6 months or any history of attempted suicide in a subject's lifetime.
• History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
• Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing; live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study.
• History of donation of blood or blood products >= 400 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.
• The subject has participated in a other clinical study or other medical research within 4 months prior to the first dosing day in the current study.
• Subject is positive Serological test for syphilis Rapid Plasma Reagin [RPR] and Treponema pallidum [TP]), Tuberculosis, human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HbsAg), Hepatitis C virus (HCV) antibody, or Human T-cell leukemia virus type 1 (HTLV-1) antibody at screening.
• Positive pre-study drug screen.
• Regular use of known drugs of abuse.
• Regular alcohol consumption within 6 months prior to the study defined as: for 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 investigators or GSK Medical Monitor, contraindicates participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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13 participants in 4 patient groups

Sequence 1: Placebo TID then 60 TID then 120 TID then 240 TID

Experimental group

Description:

The eligible subjects in this arm will receive placebo TID in TP1, GSK2982772 60 mg TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject.

Treatment:

Drug: GSK2982772

Drug: Placebo

Sequence 2: 60 TID then Placebo TID then 120 TID then 240 TID

Experimental group

Description:

The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, placebo TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject.

Treatment:

Drug: GSK2982772

Drug: Placebo

Sequence 3: 60 TID then 120 TID then Placebo TID then 240 TID

Experimental group

Description:

The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, placebo TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject.

Treatment:

Drug: GSK2982772

Drug: Placebo

Sequence 4: 60 TID then 120 TID then 240 TID then Placebo TID

Experimental group

Description:

The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, GSK2982772 240 mg TID in TP3 and placebo TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject.

Treatment:

Drug: GSK2982772

Drug: Placebo