BLU-5937: First-in-Human, Single and Multiple Doses Escalation, Safety, Tolerability, Pharmacokinetics and Food Effect

Study Overview
=================
Brief Summary
-----------------
This is a first-in-human study that will investigate the safety, tolerability and pharmacokinetics of ascending single and multiple doses of BLU-5937 using a double blind, placebo controlled, randomized, adaptive, single center study design. The influence of food on the pharmacokinetics of BLU-5037 will also be investigated.

Detailed Description
-----------------
BLU-5937 is a selective P2X3 receptor antagonist being developed for the treatment of chronic cough. This Phase 1 study will investigate the safety, tolerability and pharmacokinetics of ascending single and multiple doses of BLU-5937 administered orally to healthy volunteers.

Official Title
-----------------
A Double-Blind, Placebo Controlled, Randomized, Adaptive, First-in-Human Study to Assess, Safety, Tolerability, Pharmacokinetics and Food Effect of Single and Multiple Doses of BLU-5937 Administered Orally in Healthy Male and Female

Conditions
-----------------
Cough

Intervention / Treatment
-----------------
* Drug: BLU-5937
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult male and/or female (non-childbearing potential or, for women of childbearing potential, using 2 forms of acceptable birth control or agreed to abide by true abstinence), Age: 18 to 55 years (inclusive). Body mass index (BMI) : ≥18.5 and ≤30 kg/m². Non or ex smoker. Exclusion Criteria: Any findings from the medical examination (including medical history, physical examination, vital signs, laboratory tests and ECG) outside from normal and deemed by the investigator to be clinically significant. Use of any prescription drugs (with the exception of hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of the investigator would put into question the status of the volunteer as healthy. Volunteers who took an Investigational Product in the 28 days prior to the first study drug administration. Volunteers who donated 50 mL or more of blood in the 28 days prior to the first study drug administration. Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Doses<br>Single ascending doses, 6 dose levels | Drug: BLU-5937<br>* BLU-5937 oral tablet<br>Drug: Placebo<br>* Matching placebo to BLU-5937<br>|
| Experimental: Multiple Ascending Doses<br>Multiple ascending doses, 3 dose levels | Drug: BLU-5937<br>* BLU-5937 oral tablet<br>Drug: Placebo<br>* Matching placebo to BLU-5937<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of treatment emergent adverse events (TEAEs) | Number and severity of TEAEs collected from dosing until follow up 48 hours after last dose | up to 48 hours after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | To assess Cmax of single and multiple ascending oral doses of BLU-5937 | up to 48 hours after the last dose | 
| Area under the curve (AUC) | To assess AUC of single and multiple ascending oral doses of BLU-5937 | up to 48 hours after the last dose | 
| Maximum plasma concentration (Cmax) under fed conditions | To assess Cmax of a single oral dose of BLU-5937 under fed conditions | up to 48 hours after the last dose | 
| Area under the curve (AUC) under fed conditions | To assess AUC of a single oral dose of BLU-5937 under fed conditions | up to 48 hours after the last dose |