A Study to Evaluate Safety, Tolerability and Pharmacokinetics of MKND-201 in Healthy Volunteers
NCT Number: NCT06532942
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Healthy Volunteers
Interventions: DRUG: (Part A) MKND-201|DRUG: Placebo|DRUG: (Part B) MKND-201
Sponsor: Mannkind Corporation
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-05-28
Completion Date: 2024-10-31
Locations: Flourish Research, San Antonio, Texas, 78229, United States

Summary:
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.

Primary Outcome Measures: (Part A) Incidence of inhaled intolerability, Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia), Up to Day 9 (+/- 3 days)|(Part B) Incidence of inhaled intolerability, Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia), Up to Day 15 (+/- 3 days)|(Part A) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose, Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose, Up to Day 9 (+/- 3 days)|(Part B) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose, Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose, 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, Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement, 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, Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement, Up to Day 15 (+/- 3 days)|(Part A) Incidence of treatment-emergent adverse events (TEAEs), Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs), Up to Day 9 (+/- 3 days)|(Part B) Incidence of treatment-emergent adverse events (TEAEs), Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs), Up to Day 15 (+/- 3 days)|(Part A) Incidence of serious adverse events (SAEs), Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs), Up to Day 9 (+/- 3 days)|(Part B) Incidence of serious adverse events (SAEs), Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs), Up to Day 15 (+/- 3 days)|(Part A) Incidence of abnormal clinically significant vital signs, Incidence of abnormal clinically significant vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation rate, and body temperature), Up to Day 9 (+/- 3 days)|(Part B) Incidence of abnormal clinically significant vital signs, Incidence of abnormal clinically significant vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation rate, and body temperature), Up to Day 15 (+/- 3 days)|(Part A) Changes from baseline in liver enzymes and bilirubin, Changes from baseline in liver enzymes and bilirubin, Up to Day 9 (+/- 3 days)|(Part B) Changes from baseline in liver enzymes and bilirubin, Changes from baseline in liver enzymes and bilirubin, Up to Day 15 (+/- 3 days)|(Part A) Changes from baseline in coagulation parameters, INR and aPTT, Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT), Up to Day 9 (+/- 3 days)|(Part B) Changes from baseline in coagulation parameters, INR and aPTT, Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT), Up to Day 15 (+/- 3 days)
Secondary Outcome Measures: (Part A) Maximum plasma MNKD-201 concentration (Cmax), (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) Maximum plasma MNKD-201 concentration (Cmax), (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) Time to maximum concentration (Tmax), (Part A) Time to maximum concentration (Tmax), Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose|(Part B) Time to maximum concentration (Tmax), (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) Terminal elimination half-life (t½), (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), (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) Area under the plasma concentration-time curve (AUC) from time zero (from the start of inhalation time) to the last measurable concentration (AUC0-t), (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 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), (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) AUC from time zero (time of first inhalation) to infinity (AUC0-∞), (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-∞), (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 A) Apparent terminal elimination rate constant (Kel), (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 terminal elimination rate constant (Kel), (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 A) Apparent total body clearance (CL/F), (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), (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) Apparent volume of distribution during the terminal phase (Vz/F), (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 B) Apparent volume of distribution during the terminal phase (Vz/F), (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 A) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing, (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), predose and 5, 15, 30, 60, 90, and 120 minutes postdose|(Part B) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing, (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), predose and 5, 15, 30, 60, 90, and 120 minutes postdose