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

NCT04680429 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: RP7214-2002
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Volunteers

Keywords

DHODH

Outcome Measures

Primary Outcomes (1)

• Assessments of Adverse Events (AEs)

  Day1 - day15

Secondary Outcomes (4)

• RP7214 Cmax

  0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose

• RP7214 Tmax

  0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose

• RP7214 t½

  0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose

• RP7214 AUC0-inf

  0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose

Study Arms (2)

RP7214, Single and multiple doses

EXPERIMENTAL

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

Placebo, Single and multiple doses

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

RP7214 DRUG

Participants will receive single and multiple ascending doses of RP7214

RP7214, Single and multiple doses

Placebo DRUG

Participants will receive single and multiple ascending doses of matching placebo

Placebo, Single and multiple doses

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rhizen Pharmaceuticals SA: lead

Study Sites (2)

Rhizen Investigational Site

Las Vegas, Nevada, 89121, United States

Location

Rhizen Investigational Site

Fargo, North Dakota, 58104, United States

Location

Related Publications (1)

• 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.

  PMID: 36217901 DERIVED

MeSH Terms

Interventions

RP7214

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: December 29, 2020
• Primary Completion: July 17, 2021
• Study Completion: July 19, 2021
• Last Updated: August 18, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)