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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: RP7214; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Rhizen Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Rhizen Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects willing and able to provide informed consent for the trial
2. Male and non-childbearing female subjects aged 18 to 55 years
3. 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
4. Non-tobacco user/non-smokers or ex-smokers defined as someone who has stopped smoking cigarettes for at least 6 months.
5. Negative screen for drugs of abuse and alcohol at screening and on admission.
6. Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive.
7. 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.
8. Female subjects should be of non-childbearing potential.
9. Willing and able to understand the nature of this study, comply with the study procedures as required by the study protocol.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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.
5. Pregnant or lactating females.
6. Clinically significant abnormalities in physical examination and/or in laboratory tests (including hematology and chemistry panels, urinalysis) as assessed by the Investigator.
7. 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.
8. 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.
9. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessments of Adverse Events (AEs)	Day1 - day15

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Publications and helpful links

General Publications

• Nair A, Barde PJ, Routhu KV, Viswanadha S, Veeraraghavan S, Pak S, Peterson JA, Vakkalanka S. A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects. Br J Clin Pharmacol. 2023 Mar;89(3):1127-1138. doi: 10.1111/bcp.15562. Epub 2022 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2020
• Primary Completion (Actual): July 17, 2021
• Study Completion (Actual): July 19, 2021

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: DHODH
• Other Study ID Numbers: RP7214-2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No