Part 1 - Single Ascending Dose (SAD) Capsule Formulation:Primary objective:To investigate the safety and tolerability of single oral doses of R289 capsules in healthy subjects.Secondary objective:To characterize the pharmacokinetic (PK) profiles of…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1
Safety and tolerability parameters include: physical examination, AEs, clinical
laboratory values, vital signs, and 12-lead ECG.
Part 2 and Part 4 (Optional)
Safety and tolerability parameters include: physical examination, AEs, clinical
laboratory values, vital signs, and 12-lead ECG.
Part 3
Pharmacokinetic parameters for R289 and its active and secondary metabolites
R835 and R466 include: Cmax, tmax, t1/2, AUC0-t, AUC0-inf, AUC0-tau,
%AUCextrap, CL/F (R835 only), Vz/F (R835 only), and MR (R466/R835).
Safety and tolerability parameters include: physical examination, AEs, clinical
laboratory values, vital signs, and 12-lead ECG.
Secondary outcome
Part 1
Pharmacokinetic parameters for R289 and its active and secondary metabolites
R835 and R466 include: Cmax, tmax, t1/2, AUC0-t, AUC0-inf, AUC0-tau, AUCextrap,
CL/F (R289 only), Vz/F (R289 only), and MR in fasted and fed status.
Part 2 and Part 4 (Optional)
Pharmacokinetic parameters for R289 and its active and secondary metabolites
R835 and R466 include: Cmax, tmax, t1/2, AUC0-t, AUC0-inf, AUC0-tau,
%AUCextrap, CL/F (Day 1; R835 only), CLss/F (Day 14; R835 only), Vz/F (Day 1;
R835 only), Vss/F (Day 14; R835 only), Cssavg (Day 14), AR, MR (R466/R835).
Background summary
Rigel Pharmaceuticals, Inc. (Rigel) is developing R906289 (R289), a prodrug of
R948835 (R835), for the treatment of autoimmune and inflammatory diseases, such
as psoriasis, lupus, gouty arthritis, rheumatoid arthritis or inflammatory
bowel disease.
Study objective
Part 1 - Single Ascending Dose (SAD) Capsule Formulation:
Primary objective:
To investigate the safety and tolerability of single oral doses of R289
capsules in healthy subjects.
Secondary objective:
To characterize the pharmacokinetic (PK) profiles of single oral doses of R289
capsules, its active metabolite R835, and the secondary metabolite R466.
Part 2 - Multiple Ascending Dose (MAD) Capsule Formulation:
Primary objective:
To investigate the safety and tolerability of multiple oral doses of R289
capsules in healthy subjects.
Secondary objective:
To characterize the PK profiles of multiple oral doses of R289 capsules, its
active metabolite R835, and the secondary metabolite R466.
Part 3 - Dosage Form Relative Bioavailability (BA) and Food Effect (FE):
Primary objectives:
To investigate the bioavailability of a single oral dose of R289 administered
in tablet form relative to powder-in-capsule.
To characterize the effect of food on the PK profile of a single oral dose of
R289 in tablet form, its active metabolite R835, and the secondary metabolite
R466.
To investigate the effect of food on the safety and tolerability of a single
oral dose of R289 in tablet form.
Part 4 - Multiple Ascending Dose (MAD) Tablet Formulation (Optional):
Primary objective:
To investigate the safety and tolerability of multiple oral doses of R289
tablets in healthy subjects.
Secondary objective:
To characterize the PK profiles of multiple oral doses of R289 tablets, its
active metabolite R835, and the secondary metabolite R466.
Study design
This study is a randomized, placebo-controlled, Phase 1 study in up to four
parts: single ascending doses, and multiple ascending doses with a capsule
formulation (Part 1), and multiple ascending doses with a capsule formulation
(Part 2), bioavailability and food effect of a tablet formulation (Part 3), and
multiple ascending doses with a tablet formulation (Part 4). Part 4 will be
optional.
Parts 1, 2, and 4 will be double-blind.
Part 3 will be open-label. The bioavailability of the tablet formulation
(relative to powder-in-capsule) and effect of food will be investigated using a
single-dose, randomized, crossover, three-period design.
Intervention
R289 as 20 mg capsules or tablet
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further information.
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Listed location countries
Age
Inclusion criteria
Subjects must be able and willing to give written informed consent.
Subjects must be at least 18 years at Screening and maximum 65 years old on
date of first dose with a body mass index (BMI) of 19.0-30.0 kg/m2, inclusive
at Screening.
Female subjects must be post-menopausal or surgically sterile with negative
serum pregnancy test at Screening and a negative urine pregnancy test at
admission.
Male subjects must be willing to use adequate contraception, and to refrain
from sperm donation, from the time of dosing until 90 days after the last dose
of study drug.
Subjects must be healthy as determined by pre-study medical history, physical
examination and 12-lead ECG.
Exclusion criteria
The subject has a clinically relevant history or presence of respiratory,
gastrointestinal, renal, hepatic, hematological, lymphatic, neurological,
cardiovascular, psychiatric, musculoskeletal, immunological, dermatological,
connective tissue diseases or disorders.
The subject has a clinically relevant surgical history, including
cholecystectomy.
The subject has a history of relevant atopy.
The subject has a history of relevant drug hypersensitivity.
The subject has a history of hypertension or a blood pressure of >140 mmHg
systolic or >90 mmHg diastolic at Screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003878-46-NL |
| CCMO | NL74964.056.20 |