Thorough QT Study to Evaluate the Effects of BI 1015550 as Single Doses Following Oral Administration on Cardiac Safety Parameters (Double-blind, Randomized, Placebo-controlled, Five-period Crossover, With Open-label Moxifloxacin as Positive Control) in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- The Maximum Mean Difference Between Each Single Dose of Either a Low Dose or a High Dose of Nerandomilast and Placebo in QTcF Changes From Baseline Between 20 Min to 24 Hours After Drug Administration
研究概览
简要总结
The main objective of this trial is to evaluate the effects of a single therapeutic and a single supra-therapeutic dose of BI 1015550 following oral administration on cardiac safety parameters in healthy male and female volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The administration of BI 1015550 and placebo will be blinded while the administration of moxifloxacin will be carried out open label.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs - blood pressure (BP) and pulse rate (PR), 12-lead electrocardiogram (ECG), and clinical laboratory tests without any clinically significant abnormalities
- •Age of 18 to 50 years (inclusive)
- •Body mass index of 18.5 to 32 kg/m^2 (inclusive)
- •Signed and dated written informed consent in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
- •Either male subjects, or female subjects meet the following criteria requiring highly effective contraception from at least 30 days before the first administration of trial medication until 37 days after the last administration of the study drug:
- •Male participants must use condom plus their partner, if identified as a women of childbearing potential (WOCBP), must use an oral contraceptive or highly effective contraception
- •Female participants must be using highly effective contraception and in addition their male partner must use a condom if they are using an oral contraceptive
排除标准
- •Any finding in the medical examination (including BP, Heart rate (HR) or ECG) deviating from normal and assessed as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or heart rate outside the range of 50 to 90 beats per minute (bpm)
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, in particular, hepatic parameters (alanine transaminase, aspartate transaminase, total bilirubin) or renal parameters (creatinine) exceeding the upper limit of normal
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the investigator
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- •Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders including but not limited to depression and suicidal behaviour
- •History of clinically relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply.
研究组 & 干预措施
Sequence 1: H/M/P2/L/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: BI 1015550 (Drug)
Sequence 1: H/M/P2/L/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: Moxifloxacin (Drug)
Sequence 1: H/M/P2/L/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: Placebo (Drug)
Sequence 2: H/P1/L/P2/M
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: BI 1015550 (Drug)
Sequence 2: H/P1/L/P2/M
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: Moxifloxacin (Drug)
Sequence 2: H/P1/L/P2/M
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: Placebo (Drug)
Sequence 3: H/L/P2/M/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: BI 1015550 (Drug)
Sequence 3: H/L/P2/M/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: Moxifloxacin (Drug)
Sequence 3: H/L/P2/M/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: Placebo (Drug)
Sequence 4: M/H/L/P1/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: BI 1015550 (Drug)
Sequence 4: M/H/L/P1/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: Moxifloxacin (Drug)
Sequence 4: M/H/L/P1/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: Placebo (Drug)
Sequence 5: M/P1/L/H/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: BI 1015550 (Drug)
Sequence 5: M/P1/L/H/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: Moxifloxacin (Drug)
Sequence 5: M/P1/L/H/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: Placebo (Drug)
Sequence 6: M/P2/H/L/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: BI 1015550 (Drug)
Sequence 6: M/P2/H/L/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: Moxifloxacin (Drug)
Sequence 6: M/P2/H/L/P1
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
干预措施: Placebo (Drug)
Sequence 7: P1/M/H/P2/L
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: BI 1015550 (Drug)
Sequence 7: P1/M/H/P2/L
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: Moxifloxacin (Drug)
Sequence 7: P1/M/H/P2/L
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: Placebo (Drug)
Sequence 8: P1/P2/H/M/L
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: BI 1015550 (Drug)
Sequence 8: P1/P2/H/M/L
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: Moxifloxacin (Drug)
Sequence 8: P1/P2/H/M/L
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: Placebo (Drug)
Sequence 9: P1/L/M/H/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: BI 1015550 (Drug)
Sequence 9: P1/L/M/H/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: Moxifloxacin (Drug)
Sequence 9: P1/L/M/H/P2
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
干预措施: Placebo (Drug)
Sequence 10: P2/H/P1/M/L
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: BI 1015550 (Drug)
Sequence 10: P2/H/P1/M/L
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: Moxifloxacin (Drug)
Sequence 10: P2/H/P1/M/L
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
干预措施: Placebo (Drug)
Sequence 11: P2/P1/M/L/H
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: BI 1015550 (Drug)
Sequence 11: P2/P1/M/L/H
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: Moxifloxacin (Drug)
Sequence 11: P2/P1/M/L/H
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: Placebo (Drug)
Sequence 12: P2/L/M/P1/H
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: BI 1015550 (Drug)
Sequence 12: P2/L/M/P1/H
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: Moxifloxacin (Drug)
Sequence 12: P2/L/M/P1/H
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: Placebo (Drug)
Sequence 13: L/H/P1/P2/M
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: BI 1015550 (Drug)
Sequence 13: L/H/P1/P2/M
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: Moxifloxacin (Drug)
Sequence 13: L/H/P1/P2/M
Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: Placebo (Drug)
Sequence 14: L/M/P2/P1/H
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: BI 1015550 (Drug)
Sequence 14: L/M/P2/P1/H
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: Moxifloxacin (Drug)
Sequence 14: L/M/P2/P1/H
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
干预措施: Placebo (Drug)
Sequence 15: L/P2/P1/H/M
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: BI 1015550 (Drug)
Sequence 15: L/P2/P1/H/M
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: Moxifloxacin (Drug)
Sequence 15: L/P2/P1/H/M
Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days.
L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.
P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.
P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.
H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.
M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.
干预措施: Placebo (Drug)
结局指标
主要结局
The Maximum Mean Difference Between Each Single Dose of Either a Low Dose or a High Dose of Nerandomilast and Placebo in QTcF Changes From Baseline Between 20 Min to 24 Hours After Drug Administration
时间窗: MMRM included measurements at these time points [hours:minutes] post-drug: 0:20, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 12:00, and 24:00. MMRM values at 12:00 (low dose) and 4:30 (high dose) are shown in the table below.
QT interval corrected for heart rate (using the method of Fridericia, QTcF) changes from baseline, measured between 20 minutes and 24 hours after drug administration, were analyzed using a linear Mixed Model for Repeated Measures (MMRM). Pairwise comparison was used to compare the QTcF changes for each dose of nerandomilast (e.g., low dose, high dose) with the placebo at every time point. Mean treatment differences in the QTcF changes from baseline at each time point were estimated by the differences in the corresponding least-squares means. Two-sided 90% confidence intervals based on the t-distribution were computed for each time point. The MMRM was adjusted for the discrete fixed effects treatment, period, time, the continuous fixed effects period- and participant-baseline, the fixed effect-by-time terms, participant as random effect and time within period as a repeated effect per participant. The covariance structure for the repeated effect time was unstructured.
次要结局
- The Maximum Mean Difference Between Moxifloxacin and Placebo in QTcF Changes From Baseline Between 20 Min to 24 Hours After Drug Administration.(MMRM included measurements at these time points [hours:minutes] post-drug: 0:20, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 12:00, and 24:00. MMRM values at 3:30 (high dose moxifloxacin) are shown in the table below.)