Phase I | Study XYZ-001

Single Ascending Dose | Interim Safety & PK Readout

Aslane Mortreau · Data & AI Specialist

2025-03-01

Study Design

Objectives

  • Primary: safety and tolerability
  • Secondary: PK characterization, dose-proportionality

Design

  • Open-label, sequential dose escalation
  • 3 cohorts × 8 subjects = 24 subjects
  • Single oral dose per cohort
  • 24-hour PK sampling




Table 1. Study Cohorts and Dose Levels
Cohort Dose N Status
Cohort A (10 mg) 10 mg 8 Complete
Cohort B (30 mg) 30 mg 8 Complete
Cohort C (100 mg) 100 mg 8 Complete

Data cut-off: 2025-03-01 | Safety Analysis Set (N=24)

Key Metrics




24

Subjects enrolled

5.8 h

Mean terminal half-life

Supports once-daily dosing

2 h

Median Tmax

0

Serious adverse events

All TEAEs mild or moderate

Pharmacokinetics

NCA · Concentration-Time · Dose Proportionality

PK Profiles: Linear Scale



Figure 1. Mean Plasma Concentration-Time Profile (Linear Scale). Mean ± SD. PK Analysis Set (N=24).

PK Profiles: Semi-Log Scale



Figure 2. Mean Plasma Concentration-Time Profile (Semi-Logarithmic Scale). PK Analysis Set (N=24).

NCA Parameters



Table 2. Non-Compartmental Pharmacokinetic Parameters
Cohort N Cmax Tmax AUClast t1/2
Cohort A (10 mg) 8 0.4 (0.1) 1.0 [1.0, 2.0] 3 (0) 5.9 (0.7)
Cohort B (30 mg) 8 1.1 (0.2) 2.0 [1.0, 4.0] 10 (1) 5.8 (0.8)
Cohort C (100 mg) 8 3.7 (0.6) 2.0 [1.0, 4.0] 35 (2) 5.8 (0.7)
Cmax: ng/mL | AUClast: ng.h/mL | t1/2: h | Mean (SD) except Tmax: Median [Min, Max]

Dose proportionality

10-fold dose increase yields ~9.8-fold AUC increase. Approximate proportionality across 10-100 mg. Formal power model analysis pre-specified in SAP.

Safety

TEAEs · Severity · Laboratory Findings

Adverse Events Overview




Table 3. Overview of Treatment-Emergent Adverse Events
Cohort Any TEAE Mild Moderate Serious
Cohort A (10 mg) 4 (50%) 4 1 0
Cohort B (30 mg) 3 (38%) 3 1 0
Cohort C (100 mg) 4 (50%) 4 3 0

Key observations

  • No SAEs across all cohorts
  • All TEAEs mild or moderate
  • No dose-limiting toxicities
  • One ALT elevation in Cohort C, mild, resolved

Source: Simulated ADAE | TEAE: onset on or after first dose

TEAEs by System Organ Class



Table 4. Treatment-Emergent Adverse Events by System Organ Class and Preferred Term
Preferred Term Cohort A (10 mg) Cohort B (30 mg) Cohort C (100 mg)
Gastrointestinal disorders
Nausea 1 (12%) 1 (12%) 1 (12%)
General disorders
Fatigue 1 (12%) 0 1 (12%)
Infusion site reaction 1 (12%) 0 4 (50%)
Investigations
ALT increased 0 1 (12%) 0
Nervous system disorders
Dizziness 2 (25%) 1 (12%) 1 (12%)
Headache 0 1 (12%) 0

Conclusions

Safety · PK · Next Steps

Key Findings

Safety Favourable

  • No SAEs or DLTs at any dose level
  • All TEAEs mild or moderate
  • Single mild ALT elevation in Cohort C, resolved

PK On target

  • Dose-proportional exposure across 10-100 mg
  • Median Tmax 2 h, mean t1/2 5.8 h
  • Supports once-daily dosing

Recommendation



Next step

All cohorts met safety criteria for escalation. Recommend proceeding to multiple ascending dose phase. Dose range: 10-100 mg once daily.

Monitor

Continue ALT/AST monitoring in MAD phase. Pre-specify liver enzyme stopping rules in protocol.

Session Information

Computational Environment & Dataset Provenance
Item Value
R version 4.5.2
Platform aarch64-apple-darwin20
OS macOS Sequoia 15.6
Report rendered 2026-03-12 09:59:26.797944
Rendered by aslanemortreau
Package Versions
Package Version
haven 2.5.5
dplyr 1.1.4
tidyr 1.3.1
gt 1.1.0
ggplot2 4.0.0
scales 1.4.0
digest 0.6.37
survival 3.8.3
survminer 0.5.2
emmeans 1.11.1
mmrm 0.3.15

Reproducibility




quarto render slides-example.qmd --no-cache

# Dataset: simulated with set.seed(42)
# Key packages: dplyr, ggplot2, gt

Audit trail

In production, replace simulated data with load_verified() calls that check SHA-256 checksums at render time. Every number traces to a locked ADaM dataset.

Generated: 2026-03-12 09:59:26.870786 | Rendered by: aslanemortreau