Phase I Study of GSK2982772 in Japanese Healthy Male Participants

NCT ID: NCT03590613

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-19
• Study Completion Date: 2018-09-26

Brief Summary

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.

Conditions

Autoimmune Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

GSK2982772

Intervention Type: DRUG

GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route

Placebo

Intervention Type: DRUG

Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.

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

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.

Group Type: EXPERIMENTAL

GSK2982772

Intervention Type: DRUG

GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route

Placebo

Intervention Type: DRUG

Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.

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

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.

Group Type: EXPERIMENTAL

GSK2982772

Intervention Type: DRUG

GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route

Placebo

Intervention Type: DRUG

Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.

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

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.

Group Type: EXPERIMENTAL

GSK2982772

Intervention Type: DRUG

GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route

Placebo

Intervention Type: DRUG

Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.

Interventions

GSK2982772

GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route

Intervention Type: DRUG

Placebo

Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject must be 20 to 64 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• 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.

• 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Fukuoka, , Japan

Countries

Japan

References

Tompson DJ, Davies C, Scott NE, Cannons EP, Kostapanos M, Gross AS, Powell M, Ino H, Shimamura R, Ogura H, Nagakubo T, Igarashi H, Nakano A. Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects. Eur J Drug Metab Pharmacokinet. 2021 Jan;46(1):71-83. doi: 10.1007/s13318-020-00652-2.

Reference Type: DERIVED

PMID: 33165774 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

205037

Identifier Type: -

Identifier Source: org_study_id