Objective:

To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic biomarkers of the oral TYK2/JAK1 inhibitor SDC-1801 in healthy participants.

Approach:

• Study Design: Phase 1 trial involving 95 healthy participants in randomized single-ascending dose, multiple-ascending dose, and food-effect cohorts with doses ranging from 5 mg to 150 mg.

Key Findings:

• SDC-1801 was well tolerated with no mortality or serious adverse events.
• Mild to moderate treatment-emergent adverse events were reported, with headache being the most common.
• Evidence of pharmacologic activity was observed, including reductions in IP-10 and high-sensitivity C-reactive protein.
• Pharmacokinetic analyses indicated peak plasma concentrations at 3 to 5 hours post-administration and a half-life of 15 to 27 hours.
• Food intake modestly increased drug exposure.

Interpretation:

Limitations:

• The study was conducted in healthy participants, not in patients with inflammatory or autoimmune diseases.
• The design focused on safety and pharmacokinetics rather than clinical efficacy.
• Formulation-related differences limited the assessment of dose proportionality and pharmacokinetic linearity.

Conclusion:

Sources:

• British Journal of Clinical Pharmacology