First-in-Human Study of Oral SDC-1801 in Healthy Adults and Adults with Plaque Psoriasis (Part 3 - Food Effects)
A First-in-human, Phase I, Randomised, 4-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Food Effects, and Pharmacodynamics of Single Ascending and Multiple Ascending Oral Doses of SDC-1801 in Healthy Adults or Adults with Plaque Psoriasis (Part 3 - Healthy Adults - Food Effects)
Pharmaceutical Solutions Australia Pty Ltd
16 participants
Nov 8, 2023
Interventional
Conditions
Summary
SDC-1801 is a small molecule tyrosine kinase 2 (TYK2)/janus kinase 1 (JAK1) inhibitor entering clinical development for the treatment of participants with inflammatory diseases such as psoriasis. The nonclinical good laboratory practice (GLP) toxicology and safety pharmacology studies indicate that it is appropriate to cautiously assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SDC-1801 in the context of a well-designed, first-in-human (FIH) study. It is reasonable to say that the risk of adverse events (AEs) for JAK inhibitors are broadly similar to those for other biological disease modifying antirheumatic drug (bDMARD) classes. However, concealed within this, there are also important differences between JAK inhibitors and bDMARDs. Tofacitinib and baricitinib have AE profile characteristics that distinguish them from the other bDMARD classes, with signals including an increased risk of herpes zoster reactivation, elevation in lipids, and decreases in haemoglobin and lymphocytes (including natural killer cells). Based on available nonclinical data, SDC-1801 is a potent and selective small molecule TYK2/JAK1 inhibitor currently in development for inflammatory and autoimmune indications, and it has the potential to have an improved safety profile and similar efficacy profile compared with other JAK inhibitors and specific TYK2 inhibitors. A randomised, placebo controlled, dose-escalation, sequential group design is regarded as an appropriate standard design to initiate the cautious assessment of safety, tolerability, and PK of a new investigational product in healthy volunteers. The chosen sample sizes will provide sufficient data to make an initial assessment of the safety, tolerability, and PK of SDC-1801. In addition, the effect of food on SDC-1801 PK will be evaluated to characterise the PK of SDC-1801 in fasted and fed conditions and to guide the selection of a dosing regimen for use in further studies.
Eligibility
Inclusion Criteria14
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Able and willing to comply with the protocol requirements and to sign the informed consent form (ICF) prior to any screening evaluations.
- Healthy males and females between 18-55 years of age on date of signing ICF.
- Body mass index (BMI) between 18-32 kg/m2, inclusive.
- Participants in good health based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and fasting clinical laboratory safety tests as determined by the Investigator.
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
- alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) values less than or equal to 1.3 x upper limit of normal (ULN). Total bilirubin less than or equal to 1.3 x ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is less than or equal to ULN.
- Participant must be able and willing to comply with restrictions on prior and concomitant medication.
- Negative for severe acute respiratory syndrome coronavirus-2 infection.
- Non-smoker and not using any nicotine-containing products
- Negative screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, tricyclic antidepressants) and alcohol.
- Must agree to avoid prolonged exposure to the sun and avoid other ultraviolet light sources (e.g. tanning beds) during the study period and for 7 days after the last dose of study drug.
- Adherence to effective contraception or are proven post-menopausal
- No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) or history of untreated or inadequately treated latent or active TB infection
Exclusion Criteria39
- Known hypersensitivity to investigational medicinal product (IMP) ingredients or history of
- a significant allergic reaction to IMP ingredients as determined by the Investigator
- Positive serology for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV),
- or history of hepatitis from any cause with the exception of hepatitis A
- History of or a current immunosuppressive condition (e.g. human immunodeficiency virus
- [HIV] infection).
- Having any illness, judged by the Investigator as clinically significant, in the 3 months prior to the first dose of study drug.
- Current clinically significant infection or clinically significant infection within 6 months of
- first dose of study drug
- History of chronic or recurrent infectious disease within the last 2 years.
- Symptomatic herpes zoster or herpes simplex within 12 weeks of first dose of study drug, or more than one episode of local herpes zoster, or a history of disseminated zoster.
- Pregnant or breast feeding participants.
- Presence or sequelae of gastrointestinal, liver, or kidney (estimated creatinine clearance
- less than or equal to 80 mL/min, using the Cockcroft-Gault formula; if calculated creatinine clearance is less than or equal to 80mL/min a 24-hour urine collection may be performed to assess renal function) disease,
- History of malignancy within the past 5 years (except for basal cell carcinoma of the skin
- that has been treated and with no evidence of recurrence)
- Clinically significant abnormalities detected on 12-lead ECG
- Clinically significant abnormalities detected on vital signs.
- Significant blood loss (including blood donation [>500 mL]), or transfusion of any blood
- product within 12 weeks prior to Screening.
- Treatment with any drug known to have a potential for major organ toxicity in the last
- months before the first dose of this study drug.
- Treatment with any medication (including over-the-counter and/or prescription medicines [including hormonal replacement therapy for postmenopausal participants], dietary supplements, nutraceuticals, recreational drugs, vitamins and/or herbal supplements) within the last 2 weeks or 5 half-lives of that drug (whichever is longer) prior to the first dose of this study drug. Occasional paracetamol (maximum dose of 2 g/day and 10 g/2 weeks) is permitted for use at any time during the study.
- Vaccination with live virus, attenuated live virus, or any live viral components within the
- weeks prior to the first dose of study drug or is to receive these vaccines during study
- treatment or within 8 weeks following completion of study treatment.
- Routine household contact (during study treatment or for 8 weeks following completion of study treatment) with individuals who have received vaccination with live virus or
- attenuated live virus.
- Active drug or alcohol abuse
- Consumption of a large quantity of caffeinated coffee or tea (>6 cups per day) or equivalent.
- Consumption of grapefruit, grapefruit juice, or citrus fruits within 7 days prior to the first dose of study drug and until collection of the final PK blood sample.
- Current or previous participation in another investigational research study where the
- participant has received a drug, drug/device, or biologic within 12 weeks or 5 of its
- half-lives (whichever is longer) prior to the first dose of this study drug.
- Investigator or other study site staff who is directly involved in the conduct of the study and their relatives.
- Any condition or circumstances that in the opinion of the Investigator may make a
- participant unlikely or unable to complete the study or comply with study procedures and
- requirements.
- Previous participation in Part 1 or 2 of the study.
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Interventions
Part 3 of this study takes the form of a a randomised, open label, 2-way crossover study, consistent with United States (US) Food and Drug Administration (FDA) guidance on studies to investigate the effect of food on the bioavailability of investigational drugs. Part 3, Effects of Food on SDC-1801 in Healthy Adults Part 3 will have a randomised, open label, 2-way crossover design, and will run in parallel with Part 2 of the study. It will consist of one cohort of 16 healthy adults. Participants who have enrolled in Parts 1 or 2 of the study will not be permitted to be enrolled in Part 3 of the study. The SDC-1801 dose to be administered will be decided by the Safety Review Committee (SRC) based upon the SDC-1801 pharmacokinetic (PK) and safety profiles observed in Part 1 of the study. The dose that is selected for Part 3 of the study will have been demonstrated to be well tolerated, and the exposure at that dose would not have exceeded that seen at the no-observed-adverse-effect-level (NOAEL) (in the most sensitive toxicology species, the dog) in Part 1 of the study. Participants will be randomised in a 1:1 ratio to one of the following treatment sequences: Fed, Fasted: following a fast of at least 8 hours, one single oral dose of SDC-1801 administered 30 minutes after starting a standardised breakfast (meal completed within 30 minutes), then a washout period of at least 7 days, then one single oral dose of SDC-1801 administered after a fast of at least 8 hours. OR Fasted, Fed: one single oral dose of SDC-1801 administered after a fast of at least 8 hours, then a washout period of at least 7 days, then (following a fast of at least 8 hours) one single oral dose of SDC-1801 administered 30 minutes after starting a standardised breakfast (meal completed within 30 minutes). The composition of the standardised breakfast that patients will receive in the Fed condition is as follows: Protein - 150 calories Carbohydrate - 250 calories Fat - 500 to 600 calories Total Calories = 800-1000 calories Compliance to dosing of SDC-1801 will be confirmed by examination of each participant's mouth post-dose to confirm that each capsule has been swallowed. Participants will be administered the dose of study drug in Study Period 2 at approximately the same time as it was given in Study Period 1. The participants will be confined to the Clinical Pharmacology Unit (CPU) for Study Period 1 (from mid-afternoon or evening of Day -1 to approximately 120 hours after the first dose of study drug [i.e. Day 6]), then they will have the 7-day washout period at home. Participants will return to the CPU for Study Period 2 and be confined there from mid-afternoon or evening of Day 14 to approximately 120 hours after the second dose of study drug (i.e. Day 20). A follow-up visit will take place 14 ± 3 days after administration of the second dose of study drug. Each participant will be in the study for approximately 9 weeks (Screening Visit to Follow-up Visit) and will receive 2 doses of SDC-1801.
Locations(1)
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ACTRN12623000419662