Safety, Tolerability and Pharmacokinetics of Oral Doses of RP3128 of Rhizen Pharmaceuticals

Study Overview
=================
Brief Summary
-----------------
RP3128 is a calcium release activated calcium (CRAC) channel modulator. The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending dose(s) of RP3128 in healthy volunteers and to evaluate the effect on late phase asthmatic response to allergen challenge in patients with mild asthma.

Detailed Description
-----------------
The study consists of three parts; Part 1: single ascending dose (SAD), Part 2: multiple ascending dose (MAD) in healthy volunteers and Part 3: proof of concept (POC) study in mild asthmatics. There will be 5 cohorts in SAD and 3 cohorts in MAD, the doses used in the MAD will be based on emerging safety, tolerability and pharmacokinetics (PK) from Part 1 (SAD). POC is a randomized, placebo- controlled, double blind, two period cross-over, proof of concept study in male and female of non child bearing potential with history of mild asthma. the highest identified dose of RP3128 in Part 2 (MAD) will be considered for POC

Official Title
-----------------
A Phase I/IIa, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, and Pharmacokinetics of Single and Multiple Ascending Dose of RP3128 in HV and Effect on LAR to Allergen Challenge in Mild Asthmatics

Conditions
-----------------
Healthy Volunteers, Asthma

Intervention / Treatment
-----------------
* Drug: RP3128
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and non-childbearing female subjects (SAD/MAD) and male and non-childbearing female patients with mild asthma; Healthy subjects as determined by past medical history, vitals, physical examination and 12-lead ECG, clinical laboratory tests. Body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive, weight ≥50 kg; Non-smokers or ex-smokers Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the subject; able to comply with protocol requirements and or study procedure; Negative screen for drugs of abuse and alcohol at screening and on admission. Male subjects should agree not to donate sperm for 3 months post dose; and Female partners (of child bearing potential) of male subjects should use 2 methods of highly effective contraception for 3 months post last Additionally for POC Pre- bronchodilator Forced expiratory volume in 1 sec( FEV1) of > 70% (adjusted for age, sex and race) Steroid naïve subjects with history of mild asthma that satisfy the Global Initiative for Asthma (GINA) definition of asthma, but otherwise healthy. Exclusion Criteria: Subjects with evidence or history of clinically significant medical history. History of tuberculosis (TB) and/or a positive Tuberculin Skin Test and/or QuantiFeron- TB®-Gold test. Use of any immunotherapy within 3 months prior to screening. History of serious adverse reaction, severe hypersensitivity or allergy to any drug/drug substance (except house dust mite, pollen allergens or cat dander allergy in asthmatics) or in any other circumstance (e.g. anaphylaxis); Abnormal liver function Positive screen on hepatitis-B surface antigen (HBsAg), antibodies to the hepatitis C (HCV) or antibodies to the human immunodeficiency virus (HIV) 1,2;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RP3128<br>RP3128, A CRAC channel modulator | Drug: RP3128<br>* Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC<br>* Other names: CRAC channel modulator;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | Baseline through 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Cmax after administration of RP3128/ placebo in part 1 and part 2 | Pre-dose through 48 hours post dose | 
| Measurement of Cytokines | Levels of cytokines following LPS (lipopolysaccharide) or CD3/CD28 stimulation. | Predose and Day 7 in Part 2 | 
| Fractional Exhaled Nitric Oxide (FeNo) | Change in FeNo after administration of RP3128/ placebo in part 3 | Prechallenge to 3, 8 and 24 hours post challenge in Part 3 | 
| Area Under Effective Concentration (AUEC) | AUEC0-3h, AUEC3-8h after administration of RP3128/ placebo in part 3 | 0 to 3 hours and 3 to 8 hours post allergen challenge in Part 3 | 
| Cell Count | Absolute and % counts of sputum eosinophils and neutrophils | 8 and 24 hours post allergen challenge in Part 3 | 
| Area Under the Plasma-Concentration | AUC0-t after administration of RP3128/ placebo in part 1 and part 2 | Pre-dose through 48 hours post dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RP3128, Phase 1, Healthy volunteers