Clinical Study Report (Abbreviated) — GLPI103-101 (FIH / SAD)
| Field | Value |
|---|---|
| Document ID | CSR-101 |
| Version | 2.0 |
| Study No. | GLPI103-101 |
| Compound | GLPI-103 (GLP-1/APJ dual agonist) |
| Standard | ICH E3 (abbreviated report — early-phase) |
| Confidentiality | Confidential — portfolio use |
[MOCK — deep-knowledge assumption]No FIH data are simulated; values are illustrative and consistent with the IB (IB-001) and REF-002.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | Clinical | Initial abbreviated CSR |
| 2.0 | 2026-06-30 | Clinical | Expanded to fuller ICH E3 structure (ethics, design, disposition, PK/PD, safety) |
1. Synopsis
| Item | Description |
|---|---|
| Design | Phase 1, randomized, double-blind, placebo-controlled, Single Ascending Dose (SAD) |
| Population | Healthy adult volunteers |
| N | 40 (5 ascending-dose cohorts × 8; 6 active : 2 placebo) |
| Objectives | Safety, tolerability, PK; PD biomarker engagement (plasma apelin) |
| Doses | Sequential single doses with sentinel dosing and stopping rules |
| Primary outcome | Incidence/severity of TEAEs; PK parameters (Cmax, AUC, t½) |
2. Ethics and Study Administration
The study was conducted per the Declaration of Helsinki, ICH E6(R3) GCP, and applicable regulations, with IRB/IEC approval and written informed consent before any procedure. An independent DSMB reviewed cumulative safety before each escalation. Conducted at a single clinical pharmacology unit [MOCK].
3. Objectives
- Primary: characterize single-dose safety/tolerability and PK.
- Secondary/exploratory: PD biomarkers (plasma apelin, glucose/insulin responses); immunogenicity (anti-drug antibodies).
4. Investigational Plan
- Design: double-blind, placebo-controlled, sequential ascending single-dose cohorts. Within each cohort of 8, 6 received GLPI-103 and 2 placebo.
- Dose levels
[MOCK]: five ascending single doses spanning the projected therapeutic range, with the starting dose MABEL/NOAEL-justified (M2.4). - Sentinel dosing: the first 2 subjects per cohort (1 active : 1 placebo) were dosed and observed ≥24 h before the remainder.
- Escalation/stopping rules: escalation required DSMB review of safety; predefined stopping criteria (e.g., ≥2 subjects with the same severe related TEAE, any related SAE) governed the study.
- Eligibility: healthy adults 18–55 y, BMI 18–30 kg/m², no clinically significant disease; key exclusions: personal/family history of MTC or MEN 2, pancreatitis history.
- Assessments: intensive PK sampling over the dosing interval; continuous safety monitoring (AEs, vital signs, ECG, clinical labs).
5. Study Subjects and Disposition
40 subjects were randomized and dosed; all completed the in-unit period and the follow-up visit; no discontinuations [MOCK]. Demographics were typical of a healthy-volunteer population (predominantly younger adults, balanced sex).
6. Pharmacokinetic and Pharmacodynamic Results [MOCK]
| Parameter | Finding |
|---|---|
| Cmax / AUC | approximately dose-proportional across the tested range |
| t½ | long terminal half-life supporting once-weekly dosing |
| Accumulation | not applicable (single dose) |
| PD | dose-dependent plasma apelin engagement and a glucose-lowering signal |
| Immunogenicity | low-titre, non-neutralizing; no PK/PD impact |
7. Safety Results [MOCK]
- TEAEs: most frequent were mild, transient gastrointestinal symptoms (nausea); no dose-limiting toxicity.
- SAEs/deaths: none.
- Laboratory/ECG/vital signs: no clinically significant trends; no QT signal of concern (consistent with nonclinical hERG/telemetry).
8. Discussion and Conclusions
GLPI-103 single doses were well tolerated across the tested range, with a PK profile supporting once-weekly dosing and PD evidence of target engagement, justifying progression to multiple-dose evaluation (GLPI103-102). Findings inform the Reference Safety Information (IB-001 §7).
9. Limitations and Cross-References
As a single-dose FIH study in healthy volunteers, this report does not address efficacy, steady-state PK, or long-term safety. The single-dose PK is integrated into the population-PK model and clinical-pharmacology summary (CLINPHARM-002; M2.7.2); the cardiac-safety context (no QT/hERG liability) is detailed in CLINPHARM-003; immunogenicity is summarized in IMMUNO-001. All early-phase values are illustrative [MOCK].