A Single and Multiple Ascending and Food Effect Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects

Sponsor

Rhizen Pharmaceuticals SA (Industry)

Overall Status

Completed

CT.gov ID

NCT04680429

Collaborator

(none)

Enrollment

Locations

Arms

6.6

Actual Duration (Months)

Patients Per Site

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind study to evaluate the safety, tolerability and PK of single and multiple ascending oral doses of RP7214. The relative bioavailability in fed and fasting conditions will also be evaluated for RP7214. The study comprises three parts; Part 1: Single ascending dose, Part 2: Multiple ascending dose and Part 3: Food effect.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: RP7214 Drug: Placebo	Phase 1

Detailed Description

There are three escalating cohorts in SAD part and two escalating cohorts in MAD part. In each cohort, six eligible healthy volunteers will be randomized to receive either RP7214 or placebo in 2:1 ratio. Within each cohort, two sentinel subjects (RP7214 and Placebo) will be dosed first for assessment of safety and tolerability. The safety data of at least 48 hrs will be reviewed to confirm safety of sentinel subjects after which the remaining four subjects will be dosed. Food effect study is a randomized, 2-treatment, 2-period, 2-sequence, crossover study in 12 HVs.

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase I, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study and Food Effect Study of Oral RP7214, a DHODH Inhibitor, in Healthy Volunteers

Actual Study Start Date :

Dec 29, 2020

Actual Primary Completion Date :

Jul 17, 2021

Actual Study Completion Date :

Jul 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RP7214, Single and multiple doses In Part 1 up to 3 cohorts with single ascending doses of RP7214 at 100 mg QD, 200 mg QD and 400 mg QD. In Part 2 up to 2 cohorts with multiple ascending doses of RP7214 at 200 mg BID, 400 mg BID.	Drug: RP7214 Participants will receive single and multiple ascending doses of RP7214
Placebo Comparator: Placebo, Single and multiple doses In Part 1 up to 3 cohorts and in Part 2 up to 2 cohorts with matching placebo to RP7214 tablet	Drug: Placebo Participants will receive single and multiple ascending doses of matching placebo

Arm

Intervention/Treatment

Experimental: RP7214, Single and multiple doses

In Part 1 up to 3 cohorts with single ascending doses of RP7214 at 100 mg QD, 200 mg QD and 400 mg QD. In Part 2 up to 2 cohorts with multiple ascending doses of RP7214 at 200 mg BID, 400 mg BID.

Drug: RP7214

Participants will receive single and multiple ascending doses of RP7214

Placebo Comparator: Placebo, Single and multiple doses

In Part 1 up to 3 cohorts and in Part 2 up to 2 cohorts with matching placebo to RP7214 tablet

Drug: Placebo

Participants will receive single and multiple ascending doses of matching placebo

Outcome Measures

Primary Outcome Measures

Assessments of Adverse Events (AEs) [Day1 - day15]

Secondary Outcome Measures

RP7214 Cmax [0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose]
Maximum Observed Plasma Concentration
RP7214 Tmax [0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose]
Time for maximum plasma concentration
RP7214 t½ [0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose]
Terminal half-life
RP7214 AUC0-inf [0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose]
Area under the plasma concentration time curve from zero extrapolated to infinite time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subjects willing and able to provide informed consent for the trial
Male and non-childbearing female subjects aged 18 to 55 years
Healthy subjects as determined by pre-study medical history, vitals, physical examination and 12-lead ECG, and clinical laboratory tests within the normal reference ranges or clinically acceptable to investigator
Non-tobacco user/non-smokers or ex-smokers defined as someone who has stopped smoking cigarettes for at least 6 months.
Negative screen for drugs of abuse and alcohol at screening and on admission.
Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive.
A male subject who is able to procreate should agree to use one of the accepted contraceptives and agree to refrain from donating sperm for at least 3 months after dosing; and should not father a child during this period.
Female subjects should be of non-childbearing potential.
Willing and able to understand the nature of this study, comply with the study procedures as required by the study protocol.

Exclusion Criteria:

Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies) at the time of screening.
Positive screen for hepatitis-B surface antigen (HBsAg), antibodies to the hepatitis C (HCV) or antibodies to the human immunodeficiency virus (HIV) 1 and 2.
Subjects who received or are on Covid-19 directed prophylaxis (e.g. chloroquine or hydroxychloroquine) in last two weeks or 5x half-lives of the drug, whichever is shorter, prior to dosing.
Subjects participating in another clinical study or use of any investigational product in last 30 days or 5x half-lives of the drug, whichever is shorter, prior to dosing.
Pregnant or lactating females.
Clinically significant abnormalities in physical examination and/or in laboratory tests (including hematology and chemistry panels, urinalysis) as assessed by the Investigator.
Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulations/procedures.
Concomitant disease or condition that could interfere with the conduct of the study, or for which the treatment could interfere with the conduct of the study, or that would in the opinion of investigator, pose an unacceptable risk to the subject in this study.
Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rhizen Investigational Site	Las Vegas	Nevada	United States	89121
2	Rhizen Investigational Site	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

Rhizen Pharmaceuticals SA

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Rhizen Pharmaceuticals SA

ClinicalTrials.gov Identifier:

NCT04680429

Other Study ID Numbers:

RP7214-2002

First Posted:

Dec 23, 2020

Last Update Posted:

Aug 18, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Rhizen Pharmaceuticals SA

DHODH

Study Results

No Results Posted as of Aug 18, 2021