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

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ClinicalTrials.gov Identifier: NCT02958982
Recruitment Status : Terminated (Significant recruitment delay in POC part)
First Posted : November 8, 2016
Results First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
Rhizen Pharmaceuticals SA

Tracking Information
First Submitted Date  ICMJE October 31, 2016
First Posted Date  ICMJE November 8, 2016
Results First Submitted Date  ICMJE December 27, 2018
Results First Posted Date  ICMJE October 4, 2019
Last Update Posted Date October 4, 2019
Actual Study Start Date  ICMJE November 3, 2016
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2016)
Number of Participants With Adverse Events [ Time Frame: Baseline through 2 weeks ]
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Peak Plasma Concentration (Cmax) [ Time Frame: Pre-dose through 48 hours post dose ]
    Cmax after administration of RP3128/ placebo in part 1 and part 2
  • Measurement of Cytokines [ Time Frame: Predose and Day 7 in Part 2 ]
    Levels of cytokines following LPS (lipopolysaccharide) or CD3/CD28 stimulation.
  • Fractional Exhaled Nitric Oxide (FeNo) [ Time Frame: Prechallenge to 3, 8 and 24 hours post challenge in Part 3 ]
    Change in FeNo after administration of RP3128/ placebo in part 3
  • Area Under Effective Concentration (AUEC) [ Time Frame: 0 to 3 hours and 3 to 8 hours post allergen challenge in Part 3 ]
    AUEC0-3h, AUEC3-8h after administration of RP3128/ placebo in part 3
  • Cell Count [ Time Frame: 8 and 24 hours post allergen challenge in Part 3 ]
    Absolute and % counts of sputum eosinophils and neutrophils
  • Area Under the Plasma-Concentration [ Time Frame: Pre-dose through 48 hours post dose ]
    AUC0-t after administration of RP3128/ placebo in part 1 and part 2
Original Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2016)
  • Peak plasma concentration (Cmax) [ Time Frame: Pre-dose through 48 hours post dose ]
    Cmax after administration of RP3128/ placebo in part 1 and part 2
  • Area Under the Plasma-Concentration [ Time Frame: Pre-dose through 48 hours post dose ]
    AUC0-t after administration of RP3128/ placebo in part 1 and part 2
  • Measurement of cytokines [ Time Frame: Predose and Day 7 in Part 2 ]
    Levels of cytokines following LPS (lipopolysaccharide) or CD3/CD28 stimulation.
  • Fractional exhaled nitric oxide (FeNo) [ Time Frame: Prechallenge to 3, 8 and 24 hours post challenge in Part 3 ]
    Change in FeNo after administration of RP3128/ placebo in part 3
  • Area under effective concentration (AUEC) [ Time Frame: 0 to 3 hours and 3 to 8 hours post allergen challenge in Part 3 ]
    AUEC0-3h, AUEC3-8h after administration of RP3128/ placebo in part 3
  • Cell count [ Time Frame: 8 and 24 hours post allergen challenge in Part 3 ]
    Absolute and % counts of sputum eosinophils and neutrophils
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Pharmacokinetics of Oral Doses of RP3128 of Rhizen Pharmaceuticals
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Healthy Volunteers
  • Asthma
Intervention  ICMJE
  • Drug: RP3128
    Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC
    Other Name: CRAC channel modulator
  • Drug: Placebo
    Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC
Study Arms  ICMJE
  • Experimental: RP3128
    RP3128, A CRAC channel modulator
    Intervention: Drug: RP3128
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 21, 2018)
57
Original Estimated Enrollment  ICMJE
 (submitted: November 7, 2016)
68
Actual Study Completion Date  ICMJE February 2018
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02958982
Other Study ID Numbers  ICMJE RP3128-1601
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rhizen Pharmaceuticals SA
Study Sponsor  ICMJE Rhizen Pharmaceuticals SA
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Rhizen Pharmaceuticals SA
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP