Clinical trial NCT06532942: A Study to Evaluate Safety, Tolerability and Pharmacokinetics of MKND-201 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2024-08-01
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This first-in-human trial will be conducted in healthy adult volunteers and will investigate the safety, tolerability, and PK of MNKD-201. MNKD-201 will be evaluated over a range of doses, first in a SAD phase (Part A) and then in a MAD phase (Part B), to inform doses for further evaluation in a subsequent trial. Approximately 40 participants will be enrolled into 1 of 3 SAD cohorts and 2 MAD cohorts, 8 participants per cohort.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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).

Primary outcomes:
measure: (Part A) Incidence of inhaled intolerability
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Incidence of inhaled intolerability
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Incidence of serious adverse events (SAEs)
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Incidence of serious adverse events (SAEs)
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Incidence of abnormal clinically significant vital signs
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Incidence of abnormal clinically significant vital signs
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Changes from baseline in liver enzymes and bilirubin
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Changes from baseline in liver enzymes and bilirubin
timeFrame: Up to Day 15 (+/- 3 days)
measure: (Part A) Changes from baseline in coagulation parameters, INR and aPTT
timeFrame: Up to Day 9 (+/- 3 days)
measure: (Part B) Changes from baseline in coagulation parameters, INR and aPTT
timeFrame: Up to Day 15 (+/- 3 days)
Secondary outcomes:
measure: (Part A) Maximum plasma MNKD-201 concentration (Cmax)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) Maximum plasma MNKD-201 concentration (Cmax)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) Time to maximum concentration (Tmax)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) Time to maximum concentration (Tmax)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) Terminal elimination half-life (t½)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) Terminal elimination half-life (t½)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (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)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (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)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) AUC from time zero (time of first inhalation) to infinity (AUC0-∞)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) AUC from time zero (time of first inhalation) to infinity (AUC0-∞)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) Apparent terminal elimination rate constant (Kel)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) Apparent terminal elimination rate constant (Kel)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) Apparent total body clearance (CL/F)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) Apparent total body clearance (CL/F)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) Apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose
measure: (Part B) Apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: Day 1, predose and at multiple time points postdose up to Day 8, 12 hours after last dose on Day 7
measure: (Part A) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing
timeFrame: predose and 5, 15, 30, 60, 90, and 120 minutes postdose
measure: (Part B) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing
timeFrame: predose and 5, 15, 30, 60, 90, and 120 minutes postdose
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Flourish Research
state: Texas
Study officials:
References: