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NCT Number: NCT06532942

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of MKND-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.

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Key information

Conditions

Healthy Volunteers

Age range

40 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Flourish Research

San Antonio, Texas, 78229, United States

Location status: Recruiting

Location contact

Douglas Denham, DO

PRINCIPAL_INVESTIGATOR

Sierra Wilson

CONTACT

[email protected]

210-949-0122 ext. 208

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

(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

Placebo

Drug

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

(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

Primary outcomes

  1. (Part A) Incidence of inhaled intolerability

    Time frame: Up to Day 9 (+/- 3 days)

    Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia)

  2. (Part B) Incidence of inhaled intolerability

    Time frame: Up to Day 15 (+/- 3 days)

    Incidence of inhaled intolerability (prevalence of cough, dyspnea, bronchospasm, and dysgeusia)

  3. (Part A) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose

    Time frame: Up to Day 9 (+/- 3 days)

    Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose

  4. (Part B) Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose

    Time frame: Up to Day 15 (+/- 3 days)

    Incidence of participants with reductions in FEV1 ≥ 15% from baseline at any time postdose

  5. (Part A) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement

    Time frame: 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

  6. (Part B) Incidence of participants with reductions in FEV1 ≥ 15% following administration of a dose of study drug, compared to the corresponding predose measurement

    Time frame: 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

  7. (Part A) Incidence of treatment-emergent adverse events (TEAEs)

    Time frame: Up to Day 9 (+/- 3 days)

    Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs)

  8. (Part B) Incidence of treatment-emergent adverse events (TEAEs)

    Time frame: Up to Day 15 (+/- 3 days)

    Incidence, severity, duration, relationship to study drug, and outcome of treatment-emergent adverse events (TEAEs)

  9. (Part A) Incidence of serious adverse events (SAEs)

    Time frame: Up to Day 9 (+/- 3 days)

    Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs)

  10. (Part B) Incidence of serious adverse events (SAEs)

    Time frame: Up to Day 15 (+/- 3 days)

    Incidence, severity, duration, relationship to study drug, and outcome of serious adverse events (SAEs)

  11. (Part A) Incidence of abnormal clinically significant vital signs

    Time frame: 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)

  12. (Part B) Incidence of abnormal clinically significant vital signs

    Time frame: 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)

  13. (Part A) Changes from baseline in liver enzymes and bilirubin

    Time frame: Up to Day 9 (+/- 3 days)

    Changes from baseline in liver enzymes and bilirubin

  14. (Part B) Changes from baseline in liver enzymes and bilirubin

    Time frame: Up to Day 15 (+/- 3 days)

    Changes from baseline in liver enzymes and bilirubin

  15. (Part A) Changes from baseline in coagulation parameters, INR and aPTT

    Time frame: Up to Day 9 (+/- 3 days)

    Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT)

  16. (Part B) Changes from baseline in coagulation parameters, INR and aPTT

    Time frame: Up to Day 15 (+/- 3 days)

    Changes from baseline in coagulation parameters - international normalized ratio (INR) and activated partial thromboplastin time (aPTT)

Secondary outcomes

  1. (Part A) Maximum plasma MNKD-201 concentration (Cmax)

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

    (Part A) Maximum plasma MNKD-201 concentration (Cmax)

  2. (Part B) Maximum plasma MNKD-201 concentration (Cmax)

    Time frame: 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)

  3. (Part A) Time to maximum concentration (Tmax)

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

    (Part A) Time to maximum concentration (Tmax)

  4. (Part B) Time to maximum concentration (Tmax)

    Time frame: 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)

  5. (Part A) Terminal elimination half-life (t½)

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

    (Part A) Terminal elimination half-life (t½)

  6. (Part B) Terminal elimination half-life (t½)

    Time frame: 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)

  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)

    Time frame: 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)

  8. (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)

    Time frame: 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)

  9. (Part A) AUC from time zero (time of first inhalation) to infinity (AUC0-∞)

    Time frame: 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-∞)

  10. (Part B) AUC from time zero (time of first inhalation) to infinity (AUC0-∞)

    Time frame: 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-∞)

  11. (Part A) Apparent terminal elimination rate constant (Kel)

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

    (Part A) Apparent terminal elimination rate constant (Kel)

  12. (Part B) Apparent terminal elimination rate constant (Kel)

    Time frame: 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)

  13. (Part A) Apparent total body clearance (CL/F)

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

    (Part A) Apparent total body clearance (CL/F)

  14. (Part B) Apparent total body clearance (CL/F)

    Time frame: 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)

  15. (Part A) Apparent volume of distribution during the terminal phase (Vz/F)

    Time frame: 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)

  16. (Part B) Apparent volume of distribution during the terminal phase (Vz/F)

    Time frame: 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)

  17. (Part A) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing

    Time frame: 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)

  18. (Part B) Changes in forced expiratory volume in 1 second (FEV1) before and after dosing

    Time frame: 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Jennifer Pleitez

CONTACT

[email protected]

818-661-5000

Johanna Ulloa

CONTACT

[email protected]

818-661-5000

Sponsors and collaborators

Lead sponsor

Mannkind Corporation

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Aug 1, 2024
Registry last updated
Aug 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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