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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: (Part A) MKND-201; Drug: (Part B) MKND-201; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jennifer Pleitez; Phone Number: 818-661-5000; Email: MKC-NI-001study@mannkindcorp.com
• Study Contact Backup: Name: Johanna Ulloa; Phone Number: 818-661-5000; Email: MKC-NI-001study@mannkindcorp.com

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Flourish Research
      • Contact: Sierra Wilson; Phone Number: 208 210-949-0122; Email: SWilson@flourishresearch.com
      • Principal Investigator: Douglas Denham, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (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	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
Experimental: (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	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
Placebo Comparator: Placebo; Administered as a single dose or BID using the same number of cartridges as MKND-201 participants in the same cohort	Drug: Placebo; Participants will receive matching placebo across Part A and Part B of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(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

Outcome Measure	Measure Description	Time Frame
(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

Collaborators and Investigators

• Sponsor: Mannkind Corporation

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2024
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: MKC-NI-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No