A Phase 1, 3-part, Single (Open-label) and Multiple (Double-blind, Placebo-controlled) Oral Dose Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of LEO 32731 Formulations in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- LEO Pharma
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Part 1. Relative bioavailability (F-rel)
研究概览
简要总结
This is a phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of 4 different oral formulations of LEO 32731 in healthy subjects. The trial will be conducted in 3 parts at a single site. Each eligible subject will be enrolled into 1 group only and will participate in 3 treatment periods.
详细描述
Part 1 will evaluate the pharmacokinetics of single doses of 4 test formulations of LEO 32731 compared with a reference formulation. Part 2 will evaluate the effect of food on the pharmacokinetics of selected test formulations of LEO 32731. Part 3 will evaluate the tolerability and safety of selected test formulations of LEO 32731 after multiple dosing.
Based on data from Part 1, up to 3 formulations will be taken forward to Part 2. If none of the formulations are considered appropriate to take forward to Part 2, the trial will stop after Part 1. Similarly, based on data from Part 2, up to 2 formulations will be taken forward to Part 3. If none of the formulations are considered appropriate to take forward to Part 3, the trial will stop after Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
3-part, single (open-label) and multiple (double-blind, placebo-controlled)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group 3-2
Subjects will be dosed twice daily from Days 1-17 (morning dose only on Day 17) with LEO 32731 or placebo. The formulation depends on the outcome of Part 2.
干预措施: Placebo (Other)
Group 1-1
Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 modified release tablet; LEO 32731 blend, hard capsule; LEO 32731 API hard capsule (reference formulation).
干预措施: LEO 32731 modified release tablet (Drug)
Group 1-1
Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 modified release tablet; LEO 32731 blend, hard capsule; LEO 32731 API hard capsule (reference formulation).
干预措施: LEO 32731 blend, hard capsule (Drug)
Group 1-1
Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 modified release tablet; LEO 32731 blend, hard capsule; LEO 32731 API hard capsule (reference formulation).
干预措施: LEO 32731 API, hard capsule (Drug)
Group 1-2
Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 soft capsule; LEO 32731 gastro-resistant capsule; LEO 32731 API hard capsule (reference formulation).
干预措施: LEO 32731 API, hard capsule (Drug)
Group 1-2
Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 soft capsule; LEO 32731 gastro-resistant capsule; LEO 32731 API hard capsule (reference formulation).
干预措施: LEO 32731 soft capsule (Drug)
Group 1-2
Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 soft capsule; LEO 32731 gastro-resistant capsule; LEO 32731 API hard capsule (reference formulation).
干预措施: LEO 32731 gastro-resistant capsule (Drug)
Group 2-1
Part 2: Subjects will receive 3 doses of the same LEO 32731 formulation under different conditions, as follow (1 dose per condition/treatment period): fasted, after low-fat breakfast, after high-fat breakfast.
The formulation depends on the outcome of Part 1.
干预措施: LEO 32731 (Drug)
Group 2-2
Part 2: Subjects will receive 3 doses of the same LEO 32731 formulation under different conditions, as follow (1 dose per condition/treatment period): fasted, after low-fat breakfast, after high-fat breakfast.
The formulation depends on the outcome of Part 1.
干预措施: LEO 32731 (Drug)
Group 2-3
Part 2: Subjects will receive 3 doses of the same LEO 32731 formulation under different conditions, as follow (1 dose per condition/treatment period): fasted, after low-fat breakfast, after high-fat breakfast.
The formulation depends on the outcome of Part 1.
干预措施: LEO 32731 (Drug)
Group 3-1
Subjects will be dosed twice daily from Days 1-17 (morning dose only on Day 17) with LEO 32731 or placebo. The formulation depends on the outcome of Part 2.
干预措施: LEO 32731 (Drug)
Group 3-1
Subjects will be dosed twice daily from Days 1-17 (morning dose only on Day 17) with LEO 32731 or placebo. The formulation depends on the outcome of Part 2.
干预措施: Placebo (Other)
Group 3-2
Subjects will be dosed twice daily from Days 1-17 (morning dose only on Day 17) with LEO 32731 or placebo. The formulation depends on the outcome of Part 2.
干预措施: LEO 32731 (Drug)
结局指标
主要结局
Part 1. Relative bioavailability (F-rel)
时间窗: Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1
F-rel: AUC0 ∞ test formulations/AUC0-∞ reference formulation (derived from the statistical analysis of AUC0-∞)
Part 1. C-max
时间窗: Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1
C-max: Maximum observed plasma concentration
Part 1. t-max
时间窗: Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1
t-max: Time to reach maximum observed plasma concentration
Part 2. AUC0-∞
时间窗: Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2
AUC0-∞: Area under the plasma concentration-time curve from time 0 extrapolated to infinity
Part 2. Relative bioavailability (F-rel)
时间窗: Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2
F-rel: AUC0 ∞ test formulations/AUC0-∞ reference formulation (derived from the statistical analysis of AUC0-∞)
Part 3. Number of GI-related AEs and number of subjects with GI-related AEs during the treatment period
时间窗: From Day 1 (first dose) to Day 19 (end of treatment period) in Part 3
AEs: adverse events; GI: gastrointestinal
Part 1. AUC0-∞
时间窗: Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1
AUC0-∞: Area under the plasma concentration-time curve from time 0 extrapolated to infinity
Part 2. C-max
时间窗: Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2
C-max: Maximum observed plasma concentration
Part 2. t-max
时间窗: Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2
t-max: Time to reach maximum observed plasma concentration
次要结局
- Part 1. Number of GI-related AEs and number of subjects with GI-related AEs during each combination of treatment and period.(24 days (from first dose in first treatment period until end of last treatment period) in Part 1)
- Part 1. Number of subjects with QRS duration in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening, predose in Treatment period 1, and 48 hours postdose in Treatment period 3 in Part 1)
- Part 1. AUC0-t(Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1)
- Part 1. Number of total AEs and number of subjects with AEs during each combination of treatment and period(24 days (from first dose in first treatment period until end of last treatment period) in Part 1)
- Part 1. Number of subjects with diastolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose)
- Part 1. Number of subjects with body temperature in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose)
- Part 2. Number of subjects with diastolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 2: predose, 4 hours, 24 hours, and 72 hours postdose)
- Part 2. Number of subjects with pulse rate in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 2: predose, 4 hours, 24 hours, and 72 hours postdose)
- Part 2. Number of subjects with body temperature in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 2: predose, 4 hours, 24 hours, and 72 hours postdose)
- Part 2. Number of subjects with PR interval in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening, predose in Treatment period 1, and 72 hours postdose in Treatment period 3 in Part 2)
- Part 2. Number of subjects with QRS duration in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening, predose in Treatment period 1, and 72 hours postdose in Treatment period 3 in Part 2)
- Part 2. Number of subjects with QTcF interval in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening, predose in Treatment period 1, and 72 hours postdose in Treatment period 3 in Part 2)
- Part 2. AUC0-t(Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2)
- Part 1. Number of subjects with systolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose)
- Part 1. t1/2(Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1)
- Part 2. Number of total AEs and number of subjects with AEs during each combination of treatment and period(28 days (from first dose in first treatment period until end of last treatment period) in Part 2)
- Part 2. Number of subjects with systolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 2: predose, 4 hours, 24 hours, and 72 hours postdose)
- Part 2. t1/2(Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2)
- Part 3. AUC0-∞(Calculated using concentration data collected from predose to 16 hours postdose on Day 17 in Part 3)
- Part 3. C-max(Calculated using concentration data collected from predose to 16 hours postdose on Day 17 in Part 3)
- Part 3. t-max(Calculated using concentration data collected from predose to 16 hours postdose on Day 17 in Part 3)
- Part 3. AUC0-t(Calculated using concentration data collected from predose to 16 hours postdose on Day 17 in Part 3)
- Part 3. t1/2(Calculated using concentration data collected from predose to 16 hours postdose on Day 17 in Part 3)
- Part 3. Number of total AEs and number of subjects with AEs during the treatment period(From Day 1 (first dose) to Day 19 (end of treatment period) in Part 3)
- Part 3. Number of subjects with systolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Days 1, 3, 5, 7, 9, and 11: predose and 4 hours postdose; Day 17: predose, 4 hours, and 12 hours postdose; Day 19 (=48 hours postdose))
- Part 3. Number of subjects with diastolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Days 1, 3, 5, 7, 9, and 11: predose and 4 hours postdose; Day 17: predose, 4 hours, and 12 hours postdose; Day 19 (=48 hours postdose))
- Part 3. Number of subjects with pulse rate in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Days 1, 3, 5, 7, 9, and 11: predose and 4 hours postdose; Day 17: predose, 4 hours, and 12 hours postdose; Day 19 (=48 hours postdose))
- Part 1. Number of subjects with pulse rate in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose)
- Part 1. Number of subjects with PR interval in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening, predose in Treatment period 1, and 48 hours postdose in Treatment period 3 in Part 1)
- Part 1. Number of subjects with QTcF interval in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening, predose in Treatment period 1, and 48 hours postdose in Treatment period 3 in Part 1)
- Part 2. Number of GI-related AEs and number of subjects with GI-related AEs during each combination of treatment and period.(28 days (from first dose in first treatment period until end of last treatment period) in Part 2)
- Part 3. Number of subjects with body temperature in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Days 1, 3, 5, 7, 9, and 11: predose and 4 hours postdose; Day 17: predose, 4 hours, and 12 hours postdose; Day 19 (=48 hours postdose))
- Part 3. Number of subjects with PR interval in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Day 1: predose and 4 hours postdose; Days 3, 5, 7, 9, 11, and 17: 4 hours postdose; Day 19 (=48 hours postdose))
- Part 3. Number of subjects with QRS duration in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Day 1: predose and 4 hours postdose; Days 3, 5, 7, 9, 11, and 17: 4 hours postdose; Day 19 (=48 hours postdose))
- Part 3. Number of subjects with QTcF interval in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'(At screening and during the treatment period in Part 3: Day 1: predose and 4 hours postdose; Days 3, 5, 7, 9, 11, and 17: 4 hours postdose; Day 19 (=48 hours postdose))