Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Brensocatib
Brief summary
The main objective of the study is to evaluate the pharmacokinetics of brensocatib in participants with cystic fibrosis following once daily oral administration of study drug and to evaluate the safety of brensocatib compared to placebo in participants with cystic fibrosis (CF) over the 4-week treatment period.
Interventions
DRUGBrensocatib
Oral tablet
DRUGPlacebo
Oral tablet
Sponsors
Insmed Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be ≥18 years of age at the time of signing the informed consent. * Male or female participants with a confirmed diagnosis of CF related lung disease: 1. Percent predicted forced expiratory volume in 1 second (ppFEV1) between 40% to 90% (inclusive) at Screening Visit and at Baseline. 2. Stable CF treatment for at least 30 days before screening and willing to remain on a stable regimen throughout the treatment period. * Has a body mass index ≥18 kg/m\^2. * Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 1. Male participants, who are not sterile, with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose. 2. Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective contraception methods (i.e., methods that alone or in combination achieve \<1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose. * Female participants of childbearing potential must have a negative serum pregnancy test at Screening. * Male participants with pregnant or nonpregnant women of childbearing potential partners must use a condom.
Exclusion criteria
* Severe or unstable CF, per Investigator's judgement. * Currently being treated for allergic bronchopulmonary aspergillosis or nontuberculous mycobacteria or tuberculosis. * Active and current infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). * History of malignancy in the past 5 years, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin. * Established diagnosis of hepatitis B viral infection or positive for hepatitis B surface antigen (HBsAg) at Screening. * Established diagnosis of hepatitis C virus (HCV) infection at Screening. Participants positive for hepatitis C antibody are eligible only if HCV RNA is negative. * History of human immunodeficiency virus (HIV) infection. * Acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy (including intravenous and oral antibiotics) for pulmonary disease within 4 weeks prior to Day 1 (administration of the first dose of study drug). Participants meeting this criterion could be rescreened 4 weeks after resolution of symptoms. * History of prolonged QT/QTc interval with QTcF \>480 millisecond (msec) at Screening. * History of solid organ or hematological transplantation. * Have diagnosed periodontal disease and are either: 1. Currently treated by a dentist for this condition or 2. Expected to have periodontal disease-related procedures within the study period. * Received any live attenuated vaccine within 4 weeks prior Screening. * Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 90 days prior to Screening. * Known history of hypersensitivity to brensocatib or any of its excipients. * Use of any immunomodulatory agents within 4 weeks before the Screening Visit is prohibited during the study through end of study (including, but not limited to: bortezomib, ixazomib, thalidomide, cyclophosphamide, mycophenolate, Janus kinase inhibitors, interferon gamma (IFN-γ\], and azathioprine). * Continuous use of high-dose non-steroidal anti-inflammatory drugs (NSAIDs) is prohibited during the study through end of study. * History of alcohol, medication, or illicit drug abuse. * Current smoker, as defined by Centers for Disease Control and Prevention: An adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Brensocatib on Day 1 | Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 | — |
| Cmax of Brensocatib on Day 28 | Predose and at 0.5, 1, 2, 4, 6, 8, 24, and 168 hours postdose on Day 28 | — |
| Time to Maximum Plasma Concentration (Tmax) of Brensocatib on Day 1 | Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 | — |
| Tmax of Brensocatib on Day 28 | Predose and at 0.5, 1, 2, 4, 6, 8, 24, and 168 hours postdose on Day 28 | — |
| Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24) of Brensocatib in Plasma on Day 1 | Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 | — |
| AUC0-24 of Brensocatib in Plasma on Day 28 | Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hours postdose on Day 28 | — |
| Elimination Half-life (t1/2) of Brensocatib in Plasma on Day 28 | Predose and at 0.5, 1, 2, 4, 6, 8, 24, and 168 hours postdose on Day 28 | — |
| Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | Up to Day 56 | A TEAE is defined as any adverse event (AE) that occurred after the first dose of study investigational medicinal product (IMP) and within 28 days after the last dose of study IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Proportionality of Brensocatib for Dose Levels 10mg to 40mg Using Brensocatib Cmax After Administration of Brensocatib on Days 1 and 28 | Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose | Analysis of dose dependency for brensocatib Cmax was performed using a power law model. The logarithm of the Cmax was linearly related to the logarithm of the dose using a linear regression analysis. Slope of the regression and corresponding 90% CIs are presented. Slope (90% CI): log(PK parameter) = intercept + slope \* log(dose) + error term, for relationship between each of the dose levels. All 3 dose levels are included in the same model for the dose-exposure relationship. |
| Dose Proportionality of Brensocatib for Dose Levels 10mg to 40mg Using Brensocatib AUC0-24 After Administration of Brensocatib on Days 1 and 28 | Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hours postdose | Analysis of dose dependency for brensocatib AUC0-24 was performed using a power law model. The logarithm of the AUC0-24 was linearly related to the logarithm of the dose using a linear regression analysis. Slope of the regression and corresponding 90% CIs are presented. Slope (90% CI): log(PK parameter) = intercept + slope \* log(dose) + error term, for relationship between each of the dose levels. All 3 dose levels are included in the same model for the dose-exposure relationship. |
| AUClast of Brensocatib in Plasma on Days 1 and 28 | Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose | — |
| Dose Proportionality of Brensocatib for Dose Levels 10mg to 40mg Using Brensocatib AUClast, After Administration of Brensocatib on Days 1 and 28 | Day 1: Predose and 0.5, 1, 2, 4, 6, 8, and 24 hours postdose; Day 28: Predose and at 0.5, 1, 2, 4, 6, 8, 24 and 168 hours postdose | Analysis of dose dependency for brensocatib AUClast was performed using a power law model. The logarithm of the AUClast was linearly related to the logarithm of the dose using a linear regression analysis. Slope of the regression and corresponding 90% CIs are presented. Slope (90% CI): log(PK parameter) = intercept + slope \* log(dose) + error term, for relationship between each of the dose levels. All 3 dose levels are included in the same model for the dose-exposure relationship. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at investigational sites in the United States.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.9 Years STANDARD_DEVIATION 14.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 4 / 8 | 5 / 8 | 4 / 8 | 2 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 1 / 8 | 0 / 5 |
Outcome results
None listed