Clinical trial NCT02958982: Safety, Tolerability and Pharmacokinetics of Oral Doses of RP3128 of Rhizen Pharmaceuticals
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Healthy Volunteers
Asthma
Keywords: RP3128
Phase 1
Healthy volunteers
Lead sponsor: Rhizen Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2016-11-08
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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;

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline through 2 weeks
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: Pre-dose through 48 hours post dose
measure: Measurement of Cytokines
timeFrame: Predose and Day 7 in Part 2
measure: Fractional Exhaled Nitric Oxide (FeNo)
timeFrame: Prechallenge to 3, 8 and 24 hours post challenge in Part 3
measure: Area Under Effective Concentration (AUEC)
timeFrame: 0 to 3 hours and 3 to 8 hours post allergen challenge in Part 3
measure: Cell Count
timeFrame: 8 and 24 hours post allergen challenge in Part 3
measure: Area Under the Plasma-Concentration
timeFrame: Pre-dose through 48 hours post dose
Other outcomes:
Locations:
city: Mississauga
country: Canada
facility: Inflamax Research Inc.
state: Ontario
Study officials:
References:
citation: 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.