Healthy Volunteers
Conditions
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.
Interventions
DRUG(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
DRUGPlacebo
Participants will receive matching placebo across Part A and Part B of the study.
DRUG(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
Sponsors
Mannkind Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Part A) Incidence of inhaled intolerability | Up to Day 9 (+/- 3 days) | Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia) |
| (Part B) Incidence of inhaled intolerability | Up to Day 15 (+/- 3 days) | Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia) |
| (Part A) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose | 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 | Up to Day 15 (+/- 3 days) | Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose |
| (Part A) 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) | Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement |
| (Part B) 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) | Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement |
| (Part A) Incidence of treatment-emergent adverse events (TEAEs) | Up to Day 9 (+/- 3 days) | Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs) |
| (Part B) Incidence of treatment-emergent adverse events (TEAEs) | Up to Day 15 (+/- 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) | Up to Day 9 (+/- 3 days) | Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs) |
| (Part B) Incidence of serious adverse events (SAEs) | Up to Day 15 (+/- 3 days) | Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs) |
| (Part A) Incidence of abnormal clinically significant vital signs | 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) |
| (Part B) Incidence of abnormal clinically significant vital signs | 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 A) Changes from baseline in liver enzymes and bilirubin | Up to Day 9 (+/- 3 days) | Changes from baseline in liver enzymes and bilirubin |
| (Part B) Changes from baseline in liver enzymes and bilirubin | Up to Day 15 (+/- 3 days) | Changes from baseline in liver enzymes and bilirubin |
| (Part A) Changes from baseline in coagulation parameters, INR and aPTT | Up to Day 9 (+/- 3 days) | Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT) |
| (Part B) Changes from baseline in coagulation parameters, INR and aPTT | Up to Day 15 (+/- 3 days) | Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| (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 A) Maximum plasma MNKD-201 concentration (Cmax) |
| (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 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 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 B) Maximum plasma MNKD-201 concentration (Cmax) |
| (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) 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 B) Time to maximum concentration (Tmax) |
| (Part A) Terminal elimination half-life (t½) | Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose | (Part A) 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 B) Terminal elimination half-life (t½) |
| (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) 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 A) 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 B) AUC from time zero (time of first inhalation) to infinity (AUC0-∞) |
| (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 A) 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 B) Apparent terminal elimination rate constant (Kel) |
| (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 A) 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 B) Apparent total body clearance (CL/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 A) 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 B) Apparent volume of distribution during the terminal phase (Vz/F) |
| (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 | (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) |
Countries
United States
Contacts
Primary ContactJennifer Pleitez
Backup ContactJohanna Ulloa
Outcome results
None listed