A Study of Clofazimine Inhalation Suspension (MNKD-101) 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 Clofazimine Inhalation Suspension (MNKD-101) in Healthy Volunteers
MannKind Corporation
40 participants
Jan 27, 2022
Interventional
Conditions
Summary
This is first in human, study of Clofazimine (CFZ) inhalation suspension (MNKD-101) in healthy adult participants The study is comprised of two parts (Part A and Part B) to investigate the safety, tolerability, and pharmacokinetic of MNKD-101 Part A (Single Ascending Dose): There are total 3 cohorts in Part A of the study and each cohort will enroll approximately 8 participants Part B (Multiple Ascending Dose): There are total 2 cohorts in Part B of the study and each cohort will enroll approximately 8 participants Oversight of the study will be provided by a Safety Monitoring Committee (SMC) comprising the Investigator, the local Medical Monitor (MM), and the Sponsor’s Chief Scientific Officer (CSO). The total duration of participation in the study for each participant in Part A is up to 43 days, and up to 57 days for Part B, both inclusive of a Screening period of up to 28 days.
Eligibility
Inclusion Criteria9
- Body Mass Index (BMI) between 18.0 and 32.0 kg/m2 (inclusive). Body weight must be greater than 50 kg.
- Participants whose smoking habit in the 12 months prior to Screening included no more than 2 cigarettes or equivalent dose per week (includes e-cigarettes and other nicotine and tobacco products) can be included in the study but must be willing to abstain from smoking for one month prior to admission to the Clinical research unit (CRU) and while resident at the CRU. Thorough documentation of smoking habits is required.
- Negative test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), and Human Immunodeficiency Virus (HIV) antibody at Screening.
- Female participants must be of non-childbearing potential, as follows:
- a. At least 1 year postmenopausal (amenorrhea more than 12 months in the absence of an alternative medical cause and Follicle-stimulating hormone (FSH) greater than 40 IU/mL in women not using hormonal contraception or hormonal replacement therapy) prior to Screening.
- b. Surgically sterile (bilateral oophorectomy, hysterectomy, bilateral salpingectomy, or bilateral tubal ligation).
- To protect partners from possible exposure to study medication in semen, male participants must use a condom during the study, even if they have had a vasectomy or their partner is not of childbearing potential. Males will be required to continue to use condoms for 90 days after the last dose of MNKD-101.
- If engaged in sexual relations with a woman of childbearing potential (WOCBP), his partner must be surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from Screening until at least 135 days have passed since IP administration. Note: medically acceptable methods of contraception that may be used by the partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, and etonogestrel implant.
- Males must not donate sperm for at least 135 days after the last dose of MNKD-101.
Exclusion Criteria6
- Clinically relevant abnormal history, physical findings, Electrocardiogram (ECG), or clinical laboratory values at the Screening assessment or Day 1 that could interfere with the objectives of the study or the safety of the participant.
- Presence or history of acute or chronic illness sufficient to invalidate the participant’s participation in the study or make it unnecessarily hazardous.
- A condition that, in the opinion of the Investigator, could compromise the wellbeing of the participant or course of the study, or prevent the participant from meeting or performing any study requirements.
- Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, cancer, or history of any psychotic mental illness.
- A score on the Columbia Suicide Severity Rating Scale (C-SSRS) consistent with suicidal ideation or behavior.
- History of asthma, with the exception of resolved childhood asthma.
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Interventions
MNKD-101 is an inhalation suspension of clofazimine (CFZ) for the treatment of infections with pulmonary nontuberculous mycobacteria (NTM) both with and without cystic fibrosis. The study consists of 2 parts. Part A (Single Ascending Dose): The study will investigate the safety, tolerability, and pharmacokinetics of MNKD-101. The participants will be allocated in a randomized and double-blind manner at a ratio of 3:1 to receive MNKD-101 or placebo inhalation (6 MNKD-10 :2 placebo) In total 3 cohorts will be investigated and the dose level for each cohort may be changed based on available data and following Safety Monitoring Committee review. The maximum increment will be 30 mg CFZ (1.5ml MNKD-101) nominal per dose step and the maximal dose will be of 90 mg CFZ (4.5ml MNKD-101) nominal fill dose. Cohort A1: 30 mg CFZ (1.5ml MNKD-101) single inhaled dose using a nebulizer on Day 1 Cohort A2: 60 mg CFZ (3.0ml MNKD-101) single inhaled dose using a nebulizer on Day 1 Cohort A3: 90 mg CFZ (4.5ml MNKD-101) single inhaled dose using a nebulizer on Day 1 Each cohort consist of distinct group of participants Part B (Multiple Ascending Dose): The study will investigate the safety, tolerability, and pharmacokinetics of MNKD-101. In total 2 cohorts will be investigated and the participants will be randomized in a double-blind manner in a 3:1 ratio to receive daily doses of active or placebo treatment for 1 week Cohort B1: 30 mg CFZ (1.5ml MNKD-101) inhaled multiple ascending daily doses using a nebulizer at the same time each day from Day 1 to Day 7 Cohort B2: The inhaled multiple ascending daily doses administered using a nebulizer to be in Cohort B2 will be determined based on safety and pharmacokinetic data from Part A and Cohort B1 Each cohort consist of distinct group of participants Part B will commence after the completion of Part A of the study. The decision to commence Cohort B2 and the dose to be administered will be determined by the Safety Monitoring Committee following review of all available safety and pharmacokinetics data from Part A (SAD) and the 7-day safety and pharmacokinetic data from Cohort B1. Each inhalation will be closely monitored by an unblinded member of the study team, to ensure proper inhalation. Therefore, adherence monitoring for Part A and B is done by the study nurse observing the inhalation.
Locations(1)
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ACTRN12621001702808