Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication BRINSUPRI is indicated for the treatment of non-cystic fibrosis bronchiectasis (NCFB) in adult and pediatric patients 12 years of age and older. BRINSUPRI is a dipeptidyl peptidase 1 (DPP1) inhibitor indicated for the treatment of non-cystic fibrosis bronchiectasis in adult and pediatric patients 12 years of age and older. ( 1 ) FDA label
Also known as [14C]-brensocatib, Brensocatib Oral Solution
Brensocatib · 14 trials · 9 indications
To determine the participant clinical status on a 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome: 1. Not hospitalised, no limitations on activities 2. Not hospitalised, limitation on activities; 3. Hospitalised, not requiring supplemental oxygen; 4. Hospitalised, requiring supplemental oxygen; 5. Hospitalised, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death.
PE was defined as having 3 or more of these symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis. A severe pulmonary exacerbation was that required intravenous (IV) antibacterial drug treatment and/or hospitalization. A minimum of 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee with pulmonary physicians adjudicated reported PE events to see if they fulfil the protocol definition. The rate of PE was analyzed using the negative binomial model.
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.
Time to first pulmonary exacerbation was calculated as the number of days from the date of randomization to the date of first documentation of an exacerbation. Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis A minimum of 4 weeks must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 4 weeks from the prior exacerbation was not considered a new exacerbation. The analysis was performed using the stratified log rank test and using Kaplan Meier (KM) curves.
Pharmacokinetics of brensocatib following a single dose in healthy participants will be assessed.
The effect of clarithromycin on the single dose pharmacokinetics of brensocatib will be assessed in healthy participants.
Pharmacokinetics of brensocatib following a single dose in healthy participants will be assessed.
Comparison of the pharmacokinetics of a single dose of brensocatib in participants with hepatic impairment to that in matched healthy control participants with normal hepatic function.
Pharmacokinetics of brensocatib following a single dose in healthy participants will be assessed.
Pharmacokinetics of brensocatib following a single dose will be assessed in participants with renal impairment and in healthy participants.
Determination of the safety and tolerability of a single dose of brensocatib in participants with impaired renal function and in healthy participants.
| Arm | Type | Description |
|---|---|---|
| Brensocatib | EXPERIMENTAL | Brensocatib oral tablet, 25mg once per day for 28 days |
| Placebo | PLACEBO_COMPARATOR | Placebo oral tablet, 25mg once per day for 28 days |
| Brensocatib 10 milligrams (mg) | EXPERIMENTAL | Participants will receive brensocatib 10 mg, tablets orally, once daily, for 52 weeks. |
| Brensocatib 25 mg | EXPERIMENTAL | Participants will receive brensocatib 25 mg, tablets orally, once daily, for 52 weeks. |
| Brensocatib 40 mg | EXPERIMENTAL | Participants will receive brensocatib 40 mg tablet, orally, QD for 24 weeks along with mometasone furoate nasal spray (MFNS) by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance. |
| Brensocatib 10 mg | EXPERIMENTAL | Participants will receive brensocatib 10 mg tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance. |
| Midazolam + Brensocatib | EXPERIMENTAL | Participants will receive a single oral dose of midazolam on Day 1. From Days 2 to 13, participants will receive brensocatib administered orally, once daily. On Day 14, participants will receive a single oral dose of midazolam coadministered with a single oral dose of brensocatib. |
| Brensocatib Treatment Sequence AB | EXPERIMENTAL | Participants will receive a single dose of the pediatric oral brensocatib solution (Treatment A) on Day 1 followed by a washout period of 9 days. On Day 10, participants will receive a single dose of the oral brensocatib tablet (Treatment B). |
| Brensocatib Treatment Sequence BA | EXPERIMENTAL | Participants will receive a single dose of the oral brensocatib tablet (Treatment B) on Day 1 followed by a washout period of 9 days. On Day 10, participants will receive a single dose of the pediatric oral brensocatib solution (Treatment A). |
| Brensocatib Treatment Sequence ADBC | EXPERIMENTAL | Participants will taste and expectorate Dose 1 of each brensocatib formulation across the 4 treatment administrations (Treatments A, B, C, and D), orally on Day 1 in the sequence ADBC. |
| Brensocatib Treatment Sequence BACD | EXPERIMENTAL | Participants will taste and expectorate Dose 1 of each brensocatib formulation across the 4 treatment administrations (Treatments A, B, C, and D), orally on Day 1 in the sequence BACD. |
| Brensocatib Treatment Sequence CBDA | EXPERIMENTAL | Participants will taste and expectorate Dose 1 of each brensocatib formulation across the 4 treatment administrations (Treatments A, B, C, and D), orally on Day 1 in the sequence CBDA. |
| Brensocatib Treatment Sequence DCAB | EXPERIMENTAL | Participants will taste and expectorate Dose 1 of each brensocatib formulation across the 4 treatment administrations (Treatments A, B, C, and D), orally on Day 1 in the sequence DCAB. |
| Brensocatib + Clarithromycin | EXPERIMENTAL | Participants will receive a single oral dose of brensocatib in the morning on Days 1 and 13 after an overnight fast, and oral doses of clarithromycin, twice daily (BID), with food on Days 8 to 19. On Day 13, brensocatib will be coadministered with the morning dose of clarithromycin. Clarithromycin can be taken with food, with the exception of the morning dose on the day of coadministration with brensocatib (Day 13), which will be taken after an overnight fast. |
| Part 1: Period 1: Brensocatib | EXPERIMENTAL | Period 1: Participants will receive a single oral dose of brensocatib on Day 1 in Part 1 of the study. |
| Part 1: Period 2: Brensocatib + Rifampin | EXPERIMENTAL | Period 2: Participants will receive rifampin 600 mg once daily (QD), orally, on Days 8 to 23 along with a single oral dose of brensocatib prior to the rifampin administration on Day 17 in Part 1 of the study. |
| Part 2: Period 1: Brensocatib | EXPERIMENTAL | Period 1: Participants will receive a single oral dose of brensocatib on Day 1 in Part 2 of the study. |
| Part 2: Period 2: Brensocatib + Esomeprazole | EXPERIMENTAL | Period 2: Participants will receive esomeprazole 40 mg QD, orally, on Days 8 to 12 along with a single oral dose of brensocatib prior to the esomeprazole administration on Day 12 in Part 2 of the study. |
| Cohort 1: Brensocatib | EXPERIMENTAL | Healthy participants with normal hepatic function will receive single oral dose of brensocatib on Day 1 under fasted conditions. Healthy participants will be matched within the protocol criteria to one or more participants with hepatic impairment. |
| Cohort 2: Brensocatib | EXPERIMENTAL | Participants with mild hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 3: Brensocatib | EXPERIMENTAL | Participants with moderate hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 4: Brensocatib | EXPERIMENTAL | Participants with severe hepatic impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Part 1: Treatment Dose 1 | EXPERIMENTAL | Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 1 or placebo, once on Day 1. |
| Part 1: Treatment Dose 2 | EXPERIMENTAL | Participants (in a 3:1 ratio) will receive a single oral dose of brensocatib Dose 2 or placebo, once on Day 1. |
| Part 2 | EXPERIMENTAL | Participants will be randomized to 1 of 4 treatment sequences (ABCD, BDAC, CADB, DCBA). |
| [14C]-brensocatib | EXPERIMENTAL | Healthy participants will receive single oral dose of \[14C\]-brensocatib on Day 1 under fasted conditions. |
| Cohort 1 (Mild Impairment): Brensocatib | EXPERIMENTAL | Participants with mild renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 2 (Moderate Impairment): Brensocatib | EXPERIMENTAL | Participants with moderate renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 3 (Severe Impairment): Brensocatib | EXPERIMENTAL | Participants with severe renal impairment will receive single oral dose of brensocatib on Day 1 under fasted conditions. |
| Cohort 4 (Normal): Brensocatib | EXPERIMENTAL | Healthy participants with normal renal function will receive single oral dose of brensocatib on Day 1 under fasted conditions. Healthy participants will be matched within the protocol criteria to one or more participants with renal impairment. |
| Name | Type | Description |
|---|---|---|
| Brensocatib | DRUG | Selective, competitive, and reversible inhibitor of DPP1 |
| Placebo | DRUG | Matched placebo |
| Brensocatib 10 mg | DRUG | Oral tablet. |
| Brensocatib 25 mg | DRUG | Oral tablet. |
| Mometasone furoate nasal spray (MFNS) | DRUG | Nasal spray suspension. |
| Midazolam | DRUG | Oral solution |
| Brensocatib Oral Solution | DRUG | Brensocatib solution |
| Brensocatib Oral Tablet | DRUG | Brensocatib tablet |
| Clarithromycin | DRUG | Oral tablets. |
| Rifampin | DRUG | Oral capsules. |
| Esomeprazole | DRUG | Oral capsules. |
| Moxifloxacin | DRUG | Oral tablet. |
| [14C]-brensocatib | DRUG | Oral solution. |
Inclusion Criteria: 6.1. Inclusion criteria • Male or female * ≥16 years of age * SARS-CoV-2 infection (clinically suspected+ or laboratory confirmed\*). * Admitted to hospital as in-patient less than 96 hours prior to randomisation\^ * Illness of any duration, and at least one of the following: ...
Brensocatib is an investigational oral small molecule drug developed by Insmed Incorporated (ticker INSM). It is being studied in chronic rhinosinusitis without nasal polyps, cystic fibrosis, and other conditions. It has received FDA Breakthrough Therapy and Priority Review designations. It is not yet approved and remains in clinical development.
Brensocatib targets CTSC (cathepsin C), an enzyme involved in activating neutrophil serine proteases. By inhibiting CTSC, brensocatib aims to reduce inflammation driven by these proteases. This mechanism is being explored in neutrophil-mediated inflammatory diseases such as chronic rhinosinusitis without nasal polyps and cystic fibrosis.
Brensocatib is being developed by Insmed Incorporated, which trades under the ticker symbol INSM. Insmed is the sponsor of the clinical trials evaluating brensocatib across multiple indications, including chronic rhinosinusitis without nasal polyps and cystic fibrosis.
Brensocatib is in Phase 2 clinical development. A completed Phase 2 trial (NCT06013241) evaluated its efficacy and safety in chronic rhinosinusitis without nasal polyps. Several Phase 1 trials have also been completed. It is investigational and has not been approved by the FDA.
Brensocatib has been studied in six clinical trials. Completed trials include NCT06013241 (Phase 2 in chronic rhinosinusitis without nasal polyps), NCT06344728 and NCT06178783 (Phase 1 in healthy participants). A Phase 1 trial, NCT07859007, assessing CYP3A induction in healthy volunteers, is not yet recruiting.
Yes, [14C]-brensocatib, brensocatib oral solution, and brensocatib 10 mg are alternative names or formulations of the same drug, brensocatib. The oral solution and 10 mg refer to specific dosage forms, while [14C]-brensocatib is a radiolabeled version used in research.