A Randomized, Placebo-controlled, Double-Blind (Sponsor Unblind), Parallel Group, Single Dose, Dose Escalation Phase I Study in Sickle Cell Disease Participants, to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK4172239D
概览
- 阶段
- 1 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Hematologic Diseases
- 发起方
- GlaxoSmithKline
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Area under curve zero to time infinity (AUC 0-inf) for GSK4106401 after a single oral dose of GSK4172239D
- 状态
- 终止
- 最后更新
- 3个月前
概览
简要总结
This will be a first time in human (FTIH) study in sickle cell diseases (SCD) participants. The FTIH study is planned to evaluate the safety, tolerability, and pharmacokinetics of GSK4172239D.
The study will be composed of 3 periods for all participants (Screening, Treatment, and Follow up). Participants will be screened and, prior to first dose on Day 1, will be randomized to receive either GSK4172239D or placebo.
GSK4172239D is a prodrug that is converted in vivo into GSK4106401. This study will be a single dose, dose-escalation study. The initial dosing for all cohorts will be staggered so that 2 participants will be dosed as sentinel participants. Provided there are no safety concerns in 48 hours (h), the remaining 6 participants scheduled for the cohort may be dosed. One selected cohort of participants will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions after a washout period of a minimum of 20 days or 5 half-lives, whichever is longer, designated as the Food Effect Cohort.
研究者
入排标准
入选标准
- •Participants diagnosed with SCD not taking medication which increases gamma-globin (fetal hemoglobin).
- •Participants with SCD who have failed or not tolerated one or more approved therapies for SCD
- •Body weight greater than (\>) 50 kilogram (kg).
- •For male participants: Refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR agree to use a male condom with female partner. Agree to use an additional highly effective contraceptive method with a failure rate of less than (\<) 1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
- •For female participants: Female participants are eligible to participate if they are a woman of non-childbearing potential (WONCBP).
- •Capable of giving informed consent.
排除标准
- •Presence of active, clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug; or interfering with the interpretation of data.
- •Clinically significant abnormal blood pressure and/or history of hypertension as determined by the investigator.
- •History of clinically significant heart disease as determined by the investigator.
- •Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m\^2
- •ALT \> 3x upper limit of normal (ULN).
- •Bilirubin \> 5x ULN (isolated bilirubin \> 5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
- •Hemoglobin \< 6 gram/decalitre (g/dL).
- •Absolute neutrophil count \<1,500 / microlitre (μL).
- •Platelet count \<75,000 /μL or \>750,000 /μL.
- •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 t1/2 (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. By exception, participant may take acetaminophen (less than or equal to \[≤\] 2 g/day) up to 48h prior to the first dose of study drug.
研究组 & 干预措施
Cohort 2
Participants in this arm will receive either single dose of GSK4172239D (Dose 2) or matching placebo.
干预措施: Placebo
Cohort 1
Participants in this arm will receive either single dose of GSK4172239D (Dose 1) or matching placebo.
干预措施: GSK4172239D
Cohort 1
Participants in this arm will receive either single dose of GSK4172239D (Dose 1) or matching placebo.
干预措施: Placebo
Cohort 2
Participants in this arm will receive either single dose of GSK4172239D (Dose 2) or matching placebo.
干预措施: GSK4172239D
Cohort 3
Participants in this arm will receive either single dose of GSK4172239D (Dose 3) or matching placebo.
干预措施: GSK4172239D
Cohort 3
Participants in this arm will receive either single dose of GSK4172239D (Dose 3) or matching placebo.
干预措施: Placebo
Cohort 4
Participants in this arm will receive either single dose of GSK4172239D (Dose 4) or matching placebo.
干预措施: GSK4172239D
Cohort 4
Participants in this arm will receive either single dose of GSK4172239D (Dose 4) or matching placebo.
干预措施: Placebo
Cohort 5
Participants in this arm will receive either single dose of GSK4172239D (Dose 5) or matching placebo.
干预措施: GSK4172239D
Cohort 5
Participants in this arm will receive either single dose of GSK4172239D (Dose 5) or matching placebo.
干预措施: Placebo
Food effect cohort
One selected cohort will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions.
干预措施: GSK4172239D
Food effect cohort
One selected cohort will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions.
干预措施: Placebo
结局指标
主要结局
Area under curve zero to time infinity (AUC 0-inf) for GSK4106401 after a single oral dose of GSK4172239D
时间窗: Up to Day 3
Maximum observed plasma concentration (Cmax) for GSK4106401 after a single oral dose of GSK4172239D
时间窗: Up to Day 3
Time to Cmax (Tmax) for GSK4106401 after a single oral dose of GSK4172239D
时间窗: Up to Day 3
Half-life (t1/2) for GSK4106401 after a single oral dose of GSK4172239D
时间窗: Up to Day 3
Ratio between the fed and fasted conditions for AUC (0-inf)
时间窗: Up to Day 3
Ratio between the fed and fasted conditions for Cmax
时间窗: Up to Day 3
次要结局
- Number of participants with clinically significant changes from baseline in white blood cell (WBC)(Baseline and up to Day 7)
- Number of participants with clinically significant changes from baseline in hemoglobin(Baseline and up to Day 7)
- Number of participants with clinically significant changes from baseline in platelets count(Baseline and up to Day 7)
- Number of participants with clinically significant changes from baseline in neutrophil count(Baseline and up to Day 7)
- Number of participants with clinically significant changes from baseline in alanine transaminase (ALT)(Baseline and up to Day 7)
- Number of participants with clinically significant changes from baseline in aspartate transaminase (AST)(Baseline and up to Day 7)
- Number of participants with clinically significant changes from baseline in bilirubin(Baseline and up to Day 7)
- Number of participants with adverse event (AE) and serious adverse event (SAE)(Up to Day 7)
- Number of participants with clinically significant change from baseline in 12 lead electrocardiograms (ECG)(Baseline and up to Day 7)
- Number of participants with clinically significant change from baseline in vital signs(Baseline and up to Day 7)