A Study to Evaluate Safety, Tolerability and Pharmacokinetics of MKND-201 in Healthy Volunteers

Официальное название

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

Обзор

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.

Вмешательства

• Препарат (Part A) MKND-201
  Participants will receive single ascending doses (Target Dose, High Dose, and Very High Dose) of MKND-201 or placebo administered via oral inhalation on Day 1
• Препарат Placebo
  Participants will receive matching placebo across Part A and Part B of the study.
• Препарат (Part B) MKND-201
  Participants will receive multiple ascending doses (Target Dose and High Dose) of MKND-201 or placebo administered via oral inhalation, twice daily, from Day 1 to Day 7

Первичные конечные точки

• (Part A) Incidence of inhaled intolerability [Срок оценки: Up to Day 9 (+/- 3 days)]
• (Part B) Incidence of inhaled intolerability [Срок оценки: Up to Day 15 (+/- 3 days)]
• (Part A) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose [Срок оценки: Up to Day 9 (+/- 3 days)]
• (Part B) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose [Срок оценки: Up to Day 15 (+/- 3 days)]
• (Part A) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement [Срок оценки: Up to Day 9 (+/- 3 days)]
• (Part B) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement [Срок оценки: Up to Day 15 (+/- 3 days)]
• (Part A) Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to Day 9 (+/- 3 days)]
• (Part B) Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to Day 15 (+/- 3 days)]
• (Part A) Incidence of serious adverse events (SAEs) [Срок оценки: Up to Day 9 (+/- 3 days)]
• (Part B) Incidence of serious adverse events (SAEs) [Срок оценки: Up to Day 15 (+/- 3 days)]

Вторичные конечные точки (12)

• (Part A) Maximum plasma MNKD-201 concentration (Cmax) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose]
• (Part B) Maximum plasma MNKD-201 concentration (Cmax) [Срок оценки: 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) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose]
• (Part B) Time to maximum concentration (Tmax) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7]
• (Part A) Terminal elimination half-life (t½) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose]
• (Part B) Terminal elimination half-life (t½) [Срок оценки: 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) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose]
• (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) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7]
• (Part A) AUC from time zero (time of first inhalation) to infinity (AUC0-∞) [Срок оценки: 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-∞) [Срок оценки: 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) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose]
• (Part B) Apparent terminal elimination rate constant (Kel) [Срок оценки: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7]

Критерии участия

Критерии включения

• 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 -1. 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 -1.
• Is capable of performing spirometry, as required by the study procedures.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Flourish Research — San Antonio

Публикации

• Fares WH, Castagna M. Safety and Pharmacokinetic Data for Inhaled Administration of Nintedanib Dry Powder Inhalation for Treatment of Pulmonary Fibrotic Diseases. J Aerosol Med Pulm Drug Deliv. 2026 Aug;39(4):185-197. doi: 10.1177/19412711251414386. Epub 2026 Jan 13. PMID 42377397

Идентификаторы

NCT: NCT06532942 · MKC-NI-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗