Module 1 (US) — Administrative & US Prescribing Information — GLPI-103
| Field | Value |
|---|---|
| Document ID | M1-US |
| Version | 2.0 (full) |
| Compound | GLPI-103 (GLP-1/APJ dual agonist) |
| Region | FDA (US) — NDA Module 1 |
| Standard | eCTD US regional · 21 CFR 201.57 (PLR) · 21 CFR 208 (Medication Guide) |
| Confidentiality | Confidential |
Region-specific administrative content and the US Prescribing Information (USPI) in Physician Labeling Rule format (Highlights + Full Prescribing Information). Clinical figures trace to CSR-301 (
outputs/).[MOCK]administrative identifiers.
Change History
| Version | Date | Author | Summary |
|---|---|---|---|
| 1.0 | 2026-06-29 | Regulatory Affairs (US) | Initial Module 1 + USPI |
| 2.0 | 2026-06-29 | Regulatory Affairs (US) | Full USPI — Highlights + FPI sections 1–17 |
1.1 Cover Letter [MOCK]
Virtual Biopharma Inc. submits this New Drug Application for GLPI-103 (intravenous and oral) for the treatment of adults with type 2 diabetes mellitus inadequately controlled on metformin. Enclosed are Form FDA 356h, the proposed USPI and Medication Guide, financial disclosure certifications, and eCTD Modules 2–5.
1.2 Application Form (Form FDA 356h) — summary [MOCK]
Applicant: Virtual Biopharma Inc. · Proposed proprietary name: (TBD) · Established name: GLPI-103 · Dosage forms/strengths: solution for injection (IV, once weekly); tablet (oral, once daily) · Proposed indication: T2DM as adjunct to diet and exercise.
1.3 Administrative & Regulatory
Patent and exclusivity information, debarment certification, financial disclosure (Forms FDA 3454/3455), user-fee cover sheet, and field-copy certification are provided per 356h (not reproduced here). An environmental assessment / claim of categorical exclusion is provided per 21 CFR 25.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use GLPI-103 safely and effectively. See full prescribing information for GLPI-103.
WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning.
- In rodents, GLP-1 receptor agonists cause thyroid C-cell tumors. It is unknown whether GLPI-103 causes such tumors, including medullary thyroid carcinoma (MTC), in humans (5.1).
- GLPI-103 is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) (4).
Indications and Usage (1): GLPI-103 is a GLP-1/APJ receptor dual agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on metformin. Dosage and Administration (2): IV: 1 mg once weekly, titrated (1→2→4 mg). Oral: 2 mg once daily, titrated (2→4→8 mg). Titrate to manage gastrointestinal tolerability. Contraindications (4): Personal/family history of MTC or MEN 2; prior serious hypersensitivity. Warnings and Precautions (5): Thyroid C-cell tumors; acute pancreatitis; gastrointestinal adverse reactions; hypoglycemia with concomitant insulin secretagogues; cardiovascular/heart-rate monitoring.
FULL PRESCRIBING INFORMATION
1. Indications and Usage
GLPI-103 is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on metformin. Limitations of use: not for type 1 diabetes; not studied in patients with a history of pancreatitis.
2. Dosage and Administration
- Intravenous (Arm A regimen): initiate at 1 mg once weekly; increase to 2 mg at Week 4 and to the maintenance dose of 4 mg once weekly at Week 8.
- Oral: initiate at 2 mg once daily; increase to 4 mg at Week 4 and to the maintenance dose of 8 mg once daily at Week 8; administer per the food/water instructions.
- Titration/tolerability: if gastrointestinal symptoms are not tolerated, delay the dose increase or reduce by one level and re-attempt escalation.
- Continue background metformin.
4. Contraindications
GLPI-103 is contraindicated in patients with: a personal or family history of medullary thyroid carcinoma or MEN 2; and a prior serious hypersensitivity reaction to GLPI-103.
5. Warnings and Precautions
5.1 Thyroid C-cell tumors — see Boxed Warning; counsel patients regarding symptoms of thyroid tumors. 5.2 Acute pancreatitis — discontinue promptly if pancreatitis is suspected; do not restart if confirmed. 5.3 Gastrointestinal adverse reactions — nausea, vomiting, and diarrhea are common; severe events may cause dehydration and acute kidney injury; titrate to mitigate. 5.4 Hypoglycemia with concomitant use of insulin secretagogues or insulin — consider reducing the secretagogue/insulin dose. 5.5 Cardiovascular and heart rate — monitor heart rate and cardiovascular status given the mechanism.
6. Adverse Reactions
In the Phase 3 trial (GLPI103-301, N=900), the most common adverse reactions (≥5%) were gastrointestinal. Nausea occurred in 32.3% of patients receiving GLPI-103 IV versus 21.4% receiving the comparator (p=0.003); vomiting, diarrhea, and decreased appetite were also reported. Adverse reactions were predominantly mild to moderate; 10 serious adverse events and 2 deaths (none treatment-related) were reported in the dataset (6.1; CSR-301 §12).
7. Drug Interactions
GLPI-103 delays gastric emptying and may affect the absorption of concomitant oral medications; clinically relevant pharmacokinetic interactions are not expected based on its peptide disposition. Use with insulin secretagogues/insulin increases hypoglycemia risk (5.4).
8. Use in Specific Populations
8.1 Pregnancy — limited data; use only if the potential benefit justifies the risk. 8.2 Lactation — no data; consider benefit/risk. 8.4 Pediatric use — safety and effectiveness not established. 8.5 Geriatric use — consistent with the overall population. 8.6 Renal impairment — not studied in severe impairment (eGFR <45 excluded). 8.7 Hepatic impairment — not studied in significant impairment (ALT/AST >3×ULN excluded).
11. Description
GLPI-103 is a synthetic peptide dual agonist of the GLP-1 and apelin (APJ) receptors, supplied as a solution for intravenous injection and as a tablet for oral administration (M3).
12. Clinical Pharmacology
12.1 Mechanism of action — dual agonism of the GLP-1 and APJ receptors. 12.2 Pharmacodynamics — glucose-dependent insulinotropic and weight effects; cardiometabolic biomarker effects. 12.3 Pharmacokinetics — long half-life (once-weekly IV); oral bioavailability with permeation enhancer; proteolytic catabolism; low drug-interaction potential (M2.7.2).
13. Nonclinical Toxicology
13.1 Carcinogenesis, mutagenesis, impairment of fertility — class-appropriate thyroid C-cell monitoring; negative genotoxicity; reproductive findings limited to maternal effects (M4-2.3).
14. Clinical Studies
In GLPI103-301, GLPI-103 (IV and oral) was superior to oral semaglutide in HbA1c reduction at Week 52 (IV −0.68%, oral −0.34% versus comparator; both p<0.001), with greater weight reduction and higher responder rates (M2.7.3; CSR-301 §11).
16. How Supplied/Storage and Handling
Supplied as described in Module 3; store per label.
17. Patient Counseling Information / Medication Guide
Advise patients of the risk of thyroid tumors and symptoms of pancreatitis; counsel on managing gastrointestinal effects through titration and on hypoglycemia precautions with concomitant glucose-lowering medicines. A Medication Guide is dispensed with each prescription (21 CFR 208).