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

NCT06532942 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MKC-NI-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (16)

• (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 Outcomes (18)

• (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)

  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)

  Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose

• (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)

  Day 1, predose and at multiple time points postdose up to Day 2, 24 hours postdose

Study Arms (3)

(Part A) MKND-201 SAD

EXPERIMENTAL

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

(Part B) MKND-201 MAD

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Administered as a single dose or BID using the same number of cartridges as MKND-201 participants in the same cohort

Drug: Placebo

Interventions

(Part A) MKND-201 DRUG

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

(Part A) MKND-201 SAD

Placebo DRUG

Participants will receive matching placebo across Part A and Part B of the study.

Placebo

(Part B) MKND-201 DRUG

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

(Part B) MKND-201 MAD

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (1)

Flourish Research

San Antonio, Texas, 78229, United States

RECRUITING

Central Study Contacts

Jennifer Pleitez

CONTACT

818-661-5000; MKC-NI-001study@mannkindcorp.com

Johanna Ulloa

CONTACT

818-661-5000; MKC-NI-001study@mannkindcorp.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: August 1, 2024
• Study Start: May 28, 2024
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)