A Phase I, Open-label, Fixed-sequence, Two-period, Crossover, Drug-drug Interaction Study to Investigate the Effect of Efavirenz on the Pharmacokinetics of Ganaplacide and Lumefantrine Combination in Healthy Participants

Novartis Pharmaceuticals1 个研究点分布在 1 个国家目标入组 14 人开始时间: 2022年4月28日最近更新: 2023年1月12日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Novartis Pharmaceuticals
入组人数: 14
试验地点: 1
主要终点: Observed maximum plasma concentration (Cmax) for Ganaplacide and Lumefantrine

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study assessed the effect of multiple doses of a moderate inducer of cytochrome P450 (CYP) 3A4 (efavirenz) on the pharmacokinetics (PK) of ganaplacide and lumefantrine combination. Results from this study will provide guidance on prescribing ganaplacide and lumefantrine combination when co-administered with moderate inducers of CYP3A4.

详细描述

This is an open-label, fixed-sequence, 2-period, crossover, Drug-drug interaction (DDI) study, to evaluate the effect of multiple doses of efavirenz on the single-dose PK of ganaplacide and lumefantrine in healthy participants. The study consisted of a screening period of up to 28 days, 2 Baseline evaluations (on Day 1 of each treatment period), and 2 treatment periods which were separated by a washout period.

Participants who meet the eligibility criteria at Screening were admitted to the study site for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments were performed prior to first dosing of study treatment in each period. The participants were domiciled from the First Baseline visit until the end of the PK sampling in Period 1 and were released from the site. Participants returned to the site for the Second Baseline visit and were domiciled until the Study Completion visit in Period 2.

Participants enrolled received a single oral dose of ganaplacide and lumefantrine combination under fasting conditions on Day 1 of Period 1. In Period 2, participants received an oral dose of efavirenz q.d. under fasting conditions in the evening on Days 1 through 24 and a single dose of ganaplacide and lumefantrine combination under fasting conditions on the morning of Day 11. Between the two treatment periods, there was a washout period of at least 14 days, beginning from the last PK sample collection in Period 1 and continuing until the first dose of study treatment in Period 2.

Safety assessments (including physical examinations, ECGs, vital signs, clinical laboratory evaluations, C-SSRS, and AE and SAE monitoring) were performed during the study. The Study Completion evaluations occurred on Day 25 of Period 2, followed by a post-study safety contact (e.g. follow-up telephone call, email) approximately 30 days after the last dose of study treatment. Total duration of study was approximately 55 days from the First Baseline visit to the Study Completion visit.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Signed informed consent must be obtained prior to participation in the study.
•Healthy male and non-childbearing potential female participants 18 to 55 years of age inclusive, at Screening.
•In good health as determined by medical history, physical examination, vital signs, ECG and clinical laboratory tests, at Screening.
•Must weigh at least 50 kg with a body mass index (BMI) within the range of 18.0 to 29.9 kg/m2 inclusive, at Screening.

排除标准

•Known family history or presence of long QT syndrome.
•Known history or current clinically significant arrhythmias.
•Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 1.2 x upper limit of normal (ULN) and total bilirubin ≥ 1.5 x ULN or any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin at Screening or First Baseline.
•History of psychiatric illness.
•Score "yes" on item 4 or item 5 of the suicidal ideation section of the C-SSRS, if this ideation occurred in the past 6 months of Screening, or "yes" on any item of the suicidal behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the suicidal behavior section), if this behavior occurred in the past 2 years of Screening.
•History or presence of seizures.
•History or presence of duodenal ulcer, ulcerative colitis or Crohn's disease.
•Presence of active or uncontrolled thyroid disease.
•Additional protocol-defined inclusion / exclusion criteria may apply.

研究组 & 干预措施

Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz

Experimental

Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1.

In Period 2, participants will receive an oral dose of efavirenz q.d. in the evening on Days 1 through 24 and a single dose of ganaplacide and lumefantrine combination on the morning of Day 11.

干预措施: Ganaplacide (Drug)

Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz

Experimental

Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1.

In Period 2, participants will receive an oral dose of efavirenz q.d. in the evening on Days 1 through 24 and a single dose of ganaplacide and lumefantrine combination on the morning of Day 11.

干预措施: Lumefantrine (Combination Product)

Period 1: KAF156 + LUM566 / Period 2: KAF156 + LUM566 + Efavirenz

Experimental

Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1.

In Period 2, participants will receive an oral dose of efavirenz q.d. in the evening on Days 1 through 24 and a single dose of ganaplacide and lumefantrine combination on the morning of Day 11.

干预措施: Efavirenz (Drug)