Clinical trial NCT04680429: A Single and Multiple Ascending and Food Effect Study of RP7214, a DHODH Inhibitor in Healthy Adult Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: DHODH
Lead sponsor: Rhizen Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2020-12-23
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessments of Adverse Events (AEs)
timeFrame: Day1 - day15
Secondary outcomes:
measure: RP7214 Cmax
timeFrame: 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose
measure: RP7214 Tmax
timeFrame: 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose
measure: RP7214 t½
timeFrame: 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose
measure: RP7214 AUC0-inf
timeFrame: 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: Rhizen Investigational Site
state: Nevada
city: Fargo
country: United States
facility: Rhizen Investigational Site
state: North Dakota
Study officials:
References:
citation: 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.