📚 Part of the GLPI-103 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

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Mock / simulation document

This is a mock / simulation document, made for a portfolio and for learning. The drug (GLPI-103), the sponsor, the people, and the data are all fictional. It is not a real regulatory submission and has no clinical, legal, or regulatory standing. What is real is the shape of the thing — the document structure, the standards it follows, and the analysis methods; the content inside is illustrative.

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About this document — a plain-language guide

What it is. The Summary of Clinical Efficacy — the integrated, cross-study account of how well the drug works.

Why it exists. It pulls the efficacy results together across studies (primary and key secondary endpoints, subgroups, persistence of effect) into the concise, evidence-weighted summary a clinical reviewer relies on.

How it is produced here. It contains no new data. It is a distillation — it gathers, summarizes, and cross-references the underlying study reports and datasets into the shorter form a regulator reads first.

Format & governing standard. ICH M4E(R2) §2.7.3

Module 2.7.3 — Summary of Clinical Efficacy

Field	Value
Document ID	M273
Version	2.0 (full)
Compound	GLPI-103 (GLP-1/APJ dual agonist)
Standard	ICH M4E(R2) §2.7.3
Confidentiality	Confidential

Synthesizes efficacy across the program (Phase 2 GLPI103-201; pivotal Phase 3 GLPI103-301). Pivotal figures trace to outputs/ and are reconciled (reconcile_csr.py, 23/23). See ISE-301.

Change History

Version	Date	Author	Summary
1.0	2026-06-29	Clinical	Initial
2.0	2026-06-29	Clinical / Biostat	Full — all primary & secondary endpoints, subgroups, dose–response

1. Background & Studies Contributing

Study	Phase	N	Design	Role
GLPI103-201	2	240	dose-finding	dose–response/PoC `[MOCK]`
GLPI103-301	3	900	DB, double-dummy, active-controlled	confirmatory

2. Study Populations & Analysis Sets

Pivotal FAS N=900 (IV 300, Oral 301, Semaglutide 299); Korean adults with T2DM inadequately controlled on metformin; balanced baseline (mean age ~59–60; HbA1c 7.9–8.0%; BMI ~28–29; FPG ~12.2–12.5 mmol/L; disease duration ~10.6–12.2 yr) (CSR-301 §11.2).

3. Primary Endpoint — HbA1c CFB at Week 52 (ANCOVA, FAS)

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What 'HbA1c change from baseline' means

HbA1c is a blood marker of average sugar over the past ~3 months, so it is the standard way to judge diabetes control. 'Change from baseline at Week 52' simply asks: how much did it fall over a year, compared with the comparator drug?

Arm	LS-mean CFB (%)	95% CI
GLPI-103 IV	−2.57	−2.67, −2.47
GLPI-103 Oral	−2.23	−2.33, −2.13
Semaglutide Oral	−1.89	−1.99, −1.79

Superiority vs semaglutide: IV −0.68% (95% CI −0.81, −0.55; p<0.001); Oral −0.34% (95% CI −0.49, −0.23; p<0.001). The fixed-sequence hierarchy was satisfied (all 8 steps rejected; SAP-301 §7.3; outputs/stats/multiplicity_results.csv).

4. Longitudinal Effect (MMRM)

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Why look at every visit, not just the end

The longitudinal (MMRM) view shows the effect building visit-by-visit rather than only at the finish line, which is both more convincing and more robust to the occasional missed visit.

Progressive reduction with maintained between-arm separation through Week 52 (LS means IV −2.66, Oral −2.33, Semaglutide −1.97); onset evident by Week 4 (CSR-301 §11.4; Figure 2). The MMRM (mmrm package, unstructured covariance, Kenward-Roger DF) accommodates the 9.3% discontinuation under MAR.

5. Key Secondary & Other Endpoints (Week 52)

Endpoint	IV	Oral	Sema
Body-weight CFB (kg)	−14.5	−10.3	−7.6
≥10% weight loss, %	100.0	83.0	44.2
HbA1c <7.0%, % (completers)	94.1	94.6	86.2
FPG CFB (mmol/L)	−4.7	−4.3	−3.5
SBP CFB (mmHg)	~0	−0.8	~0

GLPI-103 produced substantially greater weight reduction and higher responder rates than semaglutide. NT-proBNP/hsCRP were pre-specified but [MOCK — not in dataset].

6. Subgroups & Consistency

Treatment benefit was consistent across baseline HbA1c (<8.5/≥8.5), BMI (<30/≥30), age (<65/≥65), and sex (CSR-301 §11.6; Figure 3), and directionally consistent with the Phase 2 dose–response.

7. Conclusions on Efficacy

GLPI-103 (IV and Oral) is superior to oral semaglutide on glycaemic control and weight, with high responder rates and consistent subgroup effects — supporting the dual GLP-1/APJ mechanism and the primary efficacy claim (TPP-001).