Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Camlipixant in Adults with Refractory or Unexplained Chronic Cough

The primary objectives of this study are to assess the effect of **BLU-5937** compared to placebo on 24-hour cough frequency in adults with **Refractory Chronic Cough**, including unexplained chronic cough, and to determine the safety of BLU-5937 versus placebo up to Week 52. Evaluating the reduction in cough frequency is clinically relevant as it directly impacts the quality of life and daily functioning of patients suffering from chronic cough. Additionally, ensuring the safety of BLU-5937 over an extended period is crucial for its potential therapeutic use.

Secondary objectives include evaluating the effects of BLU-5937 on other measures of cough frequency and patient-reported outcomes (PROs). These secondary measures provide a comprehensive understanding of the drug's impact on patient health and symptom management beyond the primary endpoints.

The clinical trial involves a total of **628 participants** diagnosed with **Refractory Chronic Cough**, including unexplained chronic cough. The study population comprises both male and female adults aged between 18 and 80 years. Participants were selected based on their ability to understand written informed consent and a diagnosis of refractory chronic cough for at least one year prior to screening. The trial includes individuals who meet specific cough frequency criteria. Female participants are eligible if they are not pregnant, not breastfeeding, and adhere to contraceptive guidance if they are of childbearing potential. The trial population includes a vulnerable population, indicating careful consideration of ethical standards. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **BLU-5937** in adult participants with **refractory chronic cough**, including unexplained chronic cough. The trial will span a total duration of 52 weeks, with an open-label extension phase. Participants will be randomly assigned to receive either BLU-5937 or a placebo, administered orally in tablet form. The primary objective is to assess the effect of BLU-5937 on 24-hour cough frequency at Week 12, as well as to evaluate the safety profile of the drug up to Week 52.

The sequence of study visits includes an initial screening visit to determine eligibility based on criteria such as age, understanding of informed consent, and a diagnosis of refractory chronic cough for at least one year prior to screening. Participants must also meet specific cough frequency criteria. The study will include follow-up visits at regular intervals to monitor cough frequency, adverse events, and overall health status. The end-of-study visit will occur at the conclusion of the 52-week period, or earlier if the participant discontinues the study.

Participant involvement is expected to last for the entire 52-week duration unless conditions arise that necessitate early termination. Such conditions include the occurrence of adverse events or serious adverse events that lead to study withdrawal, or if the participant chooses to discontinue the study treatment. The primary endpoints include the measurement of 24-hour cough frequency at Week 12 and the incidence of adverse events throughout the study period. Secondary endpoints involve changes in cough severity and quality of life assessments at specified intervals.

The clinical trial involves the administration of **BLU-5937**, an experimental medication containing the active substance **camlipixant**. This medication is presented in the form of a tablet and is chemically synthesized. The tablets are intended for **oral use**. The maximum daily dose of BLU-5937 is 1111 mg, with the same amount being the maximum total dose. The treatment period extends up to 79 days. The primary objective of the trial is to evaluate the efficacy and safety of BLU-5937 in adult participants with refractory chronic cough, including unexplained chronic cough. The trial is designed as a Phase 3, 52-week, randomized, double-blind, placebo-controlled, parallel-arm study with an open-label extension.

In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is formulated to match the appearance of the BLU-5937 tablets, being round, biconvex, plain, and white to off-white. The placebo is also administered orally, following the same dosing schedule as the experimental medication. The use of a placebo allows for the assessment of the true efficacy and safety profile of BLU-5937 by providing a baseline for comparison. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.

The efficacy of BLU-5937 in the treatment of **Refractory Chronic Cough** (RCC), including unexplained chronic cough, will be assessed in a Phase 3, 52-week, randomized, double-blind, placebo-controlled, parallel-arm study with an open-label extension. The primary efficacy endpoint is the 24-hour cough frequency at Week 12, measured using a cough monitor. Secondary endpoints include changes from baseline in the Cough Severity Visual Analog Scale (CS-VAS) and the Leicester Cough Questionnaire (LCQ) total score at Week 12, as well as objective cough frequency recordings during awake periods and 24-hour cough response at Week 12.

Data collection will occur at specified timepoints, with primary and secondary endpoints evaluated at Week 12. The study will also monitor the incidence of adverse events (AEs) and serious adverse events (SAEs) up to Week 52, including occurrences leading to study treatment discontinuations or withdrawals. The efficacy assessments will utilize validated tools such as the CS-VAS and LCQ to ensure reliable and consistent measurement of cough-related outcomes. The trial aims to provide comprehensive data on the efficacy and safety of BLU-5937 in reducing cough frequency and improving quality of life for patients with RCC.