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

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma; Healthy Volunteers
• Intervention / Treatment: Drug: RP3128; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Mississauga, Ontario, Canada, L4W 1A4
      • Inflamax Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Publications and helpful links

General Publications

• Barde PJ, Viswanadha S, Veeraraghavan S, Vakkalanka SV, Nair A. A first-in-human study to evaluate the safety, tolerability and pharmacokinetics of RP3128, an oral calcium release-activated calcium (CRAC) channel modulator in healthy volunteers. J Clin Pharm Ther. 2021 Jun;46(3):677-687. doi: 10.1111/jcpt.13322. Epub 2020 Dec 11.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2016
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (Estimate): November 8, 2016

Study Record Updates

• Last Update Posted (Actual): October 4, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Healthy volunteers; Phase 1; RP3128
• Other Study ID Numbers: RP3128-1601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No