A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Nintedanib Inhalation Powder (MNKD-201) in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- (Part A) Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
MKC-NI-001 is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled study of nintedanib inhalation powder (MNKD-201) in healthy adult volunteers. The trial consists of a Single Ascending Dose (SAD), followed by a Multiple Ascending Dose (MAD) with a primary objective to evaluate the safety, tolerability, and pharmacokinetics (PK) of MNKD-201 compared to placebo in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Is ≥40 and ≤65 years of age at the time of signing the informed consent form.
- •Has a negative urine test for selected drugs of abuse and negative alcohol test at screening and upon admission to the CRU on Day -
- •Note: Participants should not consume poppy seeds within 24 hours before urine drug screening because this can falsify the results of the opiate urine drug test.
- •Is willing to adhere to the restrictions and requirements specified in the protocol.
- •Has a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test (i.e., the virus that causes COVID-19) on Day -
- •Is capable of performing spirometry, as required by the study procedures.
排除标准
- •Has a history of significant lung disease (e.g., pulmonary fibrosis, cystic fibrosis, COPD, emphysema, chronic pulmonary infection, recent upper or lower respiratory tract infection in the prior 8 weeks, history of lung surgery or procedure, etc.)
- •Has endocrine, thyroid, or respiratory disease, diabetes mellitus, coronary heart disease, GI disease, or history of any psychotic mental illness.
- •Has a history of hepatic disease or has abnormal liver function tests (i.e., aspartate aminotransferase [AST] > 1.5 × upper limit of normal [ULN] or alanine aminotransferase [ALT] > 1.5 × ULN) at screening.
- •Has renal impairment (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2), as calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), at screening.
- •Has any history of pulmonary malignancy.
- •Has a history of substance abuse or dependency or history of recreational drug use over the last 2 years (by self-declaration).
研究组 & 干预措施
(Part A) MKND-201 SAD
Part A involves a Single Ascending Dose (SAD) study with three cohorts. In each cohort, participants will receive a single dose of MKND-201 or placebo for one day. The doses will be categorized as Target Dose, High Dose, and Very High Dose. Allocation is randomized and double-blind, maintaining a ratio of 3:1 (MKND-201:placebo). Participants will use a breath-powered inhaler, which aerosolizes the powder for lung delivery
干预措施: (Part A) MKND-201 (Drug)
(Part B) MKND-201 MAD
Part B involves a Multiple Ascending Dose (MAD) study with two cohorts. In each cohort, participants will receive MKND-201 or placebo twice daily (BID) at either the Target Dose or High Dose. Allocation is randomized 3:1 (MKND-201:placebo) and double-blind. Participants will use a breath-powered inhaler, which aerosolizes the powder for lung delivery
干预措施: (Part B) MKND-201 (Drug)
Placebo
Administered as a single dose or BID using the same number of cartridges as MKND-201 participants in the same cohort
干预措施: Placebo (Drug)
结局指标
主要结局
(Part A) Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to Day 9 (+/- 3 days)
Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs)
(Part A) Incidence of serious adverse events (SAEs)
时间窗: Up to Day 9 (+/- 3 days)
Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs)
(Part A) Incidence of inhaled intolerability
时间窗: Up to Day 9 (+/- 3 days)
Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia)
(Part B) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement
时间窗: Up to Day 15 (+/- 3 days)
Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement
(Part B) Changes from baseline in coagulation parameters, INR and aPTT
时间窗: Up to Day 15 (+/- 3 days)
Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT)
(Part A) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose
时间窗: Up to Day 9 (+/- 3 days)
Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose
(Part B) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose
时间窗: Up to Day 15 (+/- 3 days)
Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose
(Part B) Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to Day 15 (+/- 3 days)
Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs)
(Part B) Incidence of serious adverse events (SAEs)
时间窗: Up to Day 15 (+/- 3 days)
Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs)
(Part A) Changes from baseline in coagulation parameters, INR and aPTT
时间窗: Up to Day 9 (+/- 3 days)
Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT)
(Part A) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement
时间窗: Up to Day 9 (+/- 3 days)
Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement
(Part A) Changes from baseline in liver enzymes and bilirubin
时间窗: Up to Day 9 (+/- 3 days)
Changes from baseline in liver enzymes and bilirubin
(Part B) Incidence of inhaled intolerability
时间窗: Up to Day 15 (+/- 3 days)
Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia)
(Part B) Incidence of abnormal clinically significant vital signs
时间窗: Up to Day 15 (+/- 3 days)
Incidence of abnormal clinically significant vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation rate, and body temperature)
(Part B) Changes from baseline in liver enzymes and bilirubin
时间窗: Up to Day 15 (+/- 3 days)
Changes from baseline in liver enzymes and bilirubin
(Part A) Incidence of abnormal clinically significant vital signs
时间窗: Up to Day 9 (+/- 3 days)
Incidence of abnormal clinically significant vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation rate, and body temperature)
次要结局
- (Part A) Maximum plasma MNKD-201 concentration (Cmax)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part B) Apparent terminal elimination rate constant (Kel)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part B) Time to maximum concentration (Tmax)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part A) Area under the plasma concentration-time curve (AUC) from time zero (from the start of inhalation time) to the last measurable concentration (AUC0-t)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part A) Apparent terminal elimination rate constant (Kel)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part B) Apparent volume of distribution during the terminal phase (Vz/F)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part B) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing(predose and 5, 15, 30, 60, 90, and 120 minutes postdose)
- (Part A) AUC from time zero (time of first inhalation) to infinity (AUC0-∞)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part B) AUC from time zero (time of first inhalation) to infinity (AUC0-∞)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part B) Maximum plasma MNKD-201 concentration (Cmax)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part A) Apparent total body clearance (CL/F)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part B) Apparent total body clearance (CL/F)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part A) Time to maximum concentration (Tmax)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part A) Terminal elimination half-life (t½)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part B) Terminal elimination half-life (t½)(Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7)
- (Part A) Apparent volume of distribution during the terminal phase (Vz/F)(Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose)
- (Part A) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing(predose and 5, 15, 30, 60, 90, and 120 minutes postdose)