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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

Status
Terminated
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02958982
Enrollment
57
Registered
2016-11-08
Start date
2016-11-03
Completion date
2018-02-28
Last updated
2019-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma, Healthy Volunteers

Keywords

RP3128, Phase 1, Healthy volunteers

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

Interventions

DRUGRP3128

Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC

DRUGPlacebo

Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC

Sponsors

Rhizen Pharmaceuticals SA
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes

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;

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Adverse EventsBaseline through 2 weeksNumber of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Secondary

MeasureTime frameDescription
Measurement of CytokinesPredose and Day 7 in Part 2Levels of cytokines following LPS (lipopolysaccharide) or CD3/CD28 stimulation.
Fractional Exhaled Nitric Oxide (FeNo)Prechallenge to 3, 8 and 24 hours post challenge in Part 3Change in FeNo after administration of RP3128/ placebo in part 3
Peak Plasma Concentration (Cmax)Pre-dose through 48 hours post doseCmax after administration of RP3128/ placebo in part 1 and part 2
Cell Count8 and 24 hours post allergen challenge in Part 3Absolute and % counts of sputum eosinophils and neutrophils
Area Under the Plasma-ConcentrationPre-dose through 48 hours post doseAUC0-t after administration of RP3128/ placebo in part 1 and part 2
Area Under Effective Concentration (AUEC)0 to 3 hours and 3 to 8 hours post allergen challenge in Part 3AUEC0-3h, AUEC3-8h after administration of RP3128/ placebo in part 3

Countries

Canada

Participant flow

Recruitment details

Participants were recruited between 03 Nov 2016 to 05 Apr 2017 for Single Ascending Dose (SAD) study and patients were recruited between 12 May 2017 to 26 Aug 2017 for Multiple Ascending Dose (MAD) study

Pre-assignment details

There are only two groups: RP3128 and Placebo. Since this is a dose escalation study, the healthy volunteers enrolled in each cohorts are combined together and presented as study drug (RP3128) and Placebo (SAD and MAD). The proof of concept study was terminated prematurely after enrolling only one patient. Therefore, no analysis was performed.

Participants by arm

ArmCount
Pooled Placebo (SAD)
Placebo: Participants will receive single oral dose of Placebo in SAD
9
RP3128_25 mg_SAD
RP3128: Participants will receive single oral dose of 25 mg of RP3128 in SAD
3
RP3128_50 mg_SAD
RP3128: Participants will receive single oral dose of 50 mg of RP3128 in SAD
4
RP3128_100 mg_SAD
RP3128: Participants will receive single oral dose of 100 mg of RP3128 in SAD
4
RP3128_200 mg_SAD
RP3128: Participants will receive single oral dose of 200 mg of RP3128 in SAD
6
RP3128_400 mg_SAD
RP3128: Participants will receive single oral dose of 400 mg of RP3128 in SAD
6
Pooled Placebo
Placebo: Participants will receive multiple oral doses of placebo in MAD
6
RP3128_25 mg_MAD
RP3128: Participants will receive multiple oral dose of 25 mg of RP3128 in MAD
6
RP3128_100 mg_MAD
RP3128: Participants will receive multiple oral dose of 100 mg of RP3128 in MAD
6
RP3128_400 mg_MAD
RP3128: Participants will receive multiple oral dose of 400 mg of RP3128 in MAD
6
Proof of Concept
Patient received at least one dose of RP3128/placebo
1
Total57

Baseline characteristics

CharacteristicRP3128_25 mg_SADRP3128_50 mg_SADRP3128_100 mg_SADRP3128_200 mg_SADRP3128_400 mg_SADPooled PlaceboRP3128_25 mg_MADRP3128_100 mg_MADRP3128_400 mg_MADPooled Placebo (SAD)Proof of ConceptTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
3 Participants4 Participants4 Participants6 Participants6 Participants6 Participants6 Participants6 Participants6 Participants8 Participants1 Participants56 Participants
Age, Continuous36.3 Years
STANDARD_DEVIATION 4.93
36.3 Years
STANDARD_DEVIATION 9.07
31.5 Years
STANDARD_DEVIATION 6.61
38.2 Years
STANDARD_DEVIATION 8.3
34.7 Years
STANDARD_DEVIATION 9.42
36.7 Years
STANDARD_DEVIATION 4.59
29.5 Years
STANDARD_DEVIATION 6.92
33.2 Years
STANDARD_DEVIATION 3.43
36.5 Years
STANDARD_DEVIATION 5.39
29.4 Years
STANDARD_DEVIATION 8.26
32.0 Years
STANDARD_DEVIATION 0
33.6 Years
STANDARD_DEVIATION 7.32
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants1 Participants0 Participants1 Participants0 Participants1 Participants3 Participants3 Participants2 Participants2 Participants0 Participants16 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
0 Participants3 Participants4 Participants5 Participants6 Participants5 Participants3 Participants3 Participants4 Participants7 Participants1 Participants41 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Asian
1 Participants1 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants1 Participants0 Participants1 Participants6 Participants
Race (NIH/OMB)
Black or African American
0 Participants1 Participants0 Participants2 Participants4 Participants2 Participants1 Participants2 Participants1 Participants2 Participants0 Participants15 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
2 Participants2 Participants3 Participants3 Participants2 Participants3 Participants5 Participants3 Participants4 Participants6 Participants0 Participants33 Participants
Region of Enrollment
Canada
3 participants4 participants4 participants6 participants6 participants6 participants6 participants6 participants6 participants9 participants1 participants57 participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
3 Participants4 Participants4 Participants6 Participants6 Participants6 Participants6 Participants6 Participants6 Participants9 Participants1 Participants57 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
EG010
affected / at risk
deaths
Total, all-cause mortality
0 / 90 / 30 / 40 / 40 / 60 / 60 / 60 / 60 / 60 / 60 / 1
other
Total, other adverse events
4 / 91 / 32 / 44 / 42 / 64 / 63 / 61 / 60 / 62 / 60 / 1
serious
Total, serious adverse events
0 / 90 / 30 / 40 / 40 / 60 / 60 / 60 / 60 / 60 / 60 / 1

Outcome results

Primary

Number of Participants With Adverse Events

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Time frame: Baseline through 2 weeks

Population: There are only two groups: RP3128 and Placebo. Since this is a dose escalation study, the healthy volunteers enrolled in each cohorts are combined together and presented as study drug (RP3128) and Placebo for, the baseline characteristics and outcomes in both SAD and MAD.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Pooled Placebo (SAD)Number of Participants With Adverse Events4 Participants
RP3128_25 mg_SADNumber of Participants With Adverse Events1 Participants
RP3128_50 mg_SADNumber of Participants With Adverse Events2 Participants
RP3128_100 mg_SADNumber of Participants With Adverse Events4 Participants
RP3128_200 mg_SADNumber of Participants With Adverse Events2 Participants
RP3128_400 mg_SADNumber of Participants With Adverse Events4 Participants
Pooled Placebo (MAD)Number of Participants With Adverse Events3 Participants
RP3128_25 mg_MADNumber of Participants With Adverse Events1 Participants
RP3128_100 mg_MADNumber of Participants With Adverse Events0 Participants
RP3128_400 mg_MADNumber of Participants With Adverse Events2 Participants
Proof of ConceptNumber of Participants With Adverse Events0 Participants
Secondary

Area Under Effective Concentration (AUEC)

AUEC0-3h, AUEC3-8h after administration of RP3128/ placebo in part 3

Time frame: 0 to 3 hours and 3 to 8 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

Time frame: Pre-dose through 48 hours post dose

ArmMeasureValue (MEAN)Dispersion
Pooled Placebo (SAD)Area Under the Plasma-Concentration0 micrograms*hours/mLStandard Deviation 0
RP3128_25 mg_SADArea Under the Plasma-Concentration8.821 micrograms*hours/mLStandard Deviation 0.47
RP3128_50 mg_SADArea Under the Plasma-Concentration10.766 micrograms*hours/mLStandard Deviation 3.884
RP3128_100 mg_SADArea Under the Plasma-Concentration30.340 micrograms*hours/mLStandard Deviation 9.968
RP3128_200 mg_SADArea Under the Plasma-Concentration37.011 micrograms*hours/mLStandard Deviation 14.56
RP3128_400 mg_SADArea Under the Plasma-Concentration94.227 micrograms*hours/mLStandard Deviation 39.29
Pooled Placebo (MAD)Area Under the Plasma-Concentration0 micrograms*hours/mLStandard Deviation 0
RP3128_25 mg_MADArea Under the Plasma-Concentration7.934 micrograms*hours/mLStandard Deviation 1.23
RP3128_100 mg_MADArea Under the Plasma-Concentration31.034 micrograms*hours/mLStandard Deviation 19.71
RP3128_400 mg_MADArea Under the Plasma-Concentration61.821 micrograms*hours/mLStandard Deviation 39.023
Proof of ConceptArea Under the Plasma-Concentration0 micrograms*hours/mLStandard Deviation 0
Secondary

Cell Count

Absolute and % counts of sputum eosinophils and neutrophils

Time frame: 8 and 24 hours post allergen challenge in Part 3

Secondary

Fractional Exhaled Nitric Oxide (FeNo)

Change in FeNo after administration of RP3128/ placebo in part 3

Time frame: Prechallenge to 3, 8 and 24 hours post challenge in Part 3

Secondary

Measurement of Cytokines

Levels of cytokines following LPS (lipopolysaccharide) or CD3/CD28 stimulation.

Time frame: Predose and Day 7 in Part 2

Secondary

Peak Plasma Concentration (Cmax)

Cmax after administration of RP3128/ placebo in part 1 and part 2

Time frame: Pre-dose through 48 hours post dose

ArmMeasureValue (MEAN)Dispersion
Pooled Placebo (SAD)Peak Plasma Concentration (Cmax)0 micrograms/mLStandard Deviation 0
RP3128_25 mg_SADPeak Plasma Concentration (Cmax)0.171 micrograms/mLStandard Deviation 0.041
RP3128_50 mg_SADPeak Plasma Concentration (Cmax)0.305 micrograms/mLStandard Deviation 0.075
RP3128_100 mg_SADPeak Plasma Concentration (Cmax)0.561 micrograms/mLStandard Deviation 0.12
RP3128_200 mg_SADPeak Plasma Concentration (Cmax)0.64 micrograms/mLStandard Deviation 0.29
RP3128_400 mg_SADPeak Plasma Concentration (Cmax)0.915 micrograms/mLStandard Deviation 0.41
Pooled Placebo (MAD)Peak Plasma Concentration (Cmax)0 micrograms/mLStandard Deviation 0
RP3128_25 mg_MADPeak Plasma Concentration (Cmax)0.533 micrograms/mLStandard Deviation 0.1
RP3128_100 mg_MADPeak Plasma Concentration (Cmax)2.034 micrograms/mLStandard Deviation 1.11
RP3128_400 mg_MADPeak Plasma Concentration (Cmax)3.95 micrograms/mLStandard Deviation 2.16
Proof of ConceptPeak Plasma Concentration (Cmax)0 micrograms/mLStandard Deviation 0

Source: ClinicalTrials.gov · Data processed: Feb 16, 2026