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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02958982
• Other study ID #: RP3128-1601
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 3, 2016
• Est. completion date: February 2018

Study information

• Verified date: September 2019
• Source: Rhizen Pharmaceuticals SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 57
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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;

Related Conditions & MeSH terms

• Asthma
• Healthy Volunteers

Intervention

Drug:
• RP3128
Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC
• Placebo
Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC

Locations

Country	Name	City	State
Canada	Inflamax Research Inc.	Mississauga	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Rhizen Pharmaceuticals SA

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Peak Plasma Concentration (Cmax)	Cmax after administration of RP3128/ placebo in part 1 and part 2	Pre-dose through 48 hours post dose
Secondary	Measurement of Cytokines	Levels of cytokines following LPS (lipopolysaccharide) or CD3/CD28 stimulation.	Predose and Day 7 in Part 2
Secondary	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
Secondary	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
Secondary	Cell Count	Absolute and % counts of sputum eosinophils and neutrophils	8 and 24 hours post allergen challenge in Part 3
Secondary	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