CLINICAL TRIALS PROFILE FOR ERTUGLIFLOZIN; METFORMIN HYDROCHLORIDE

All Clinical Trials for Ertugliflozin; Metformin Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01986855 ↗	A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)	Completed	Pfizer	Phase 3	2013-12-02	This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The duration of this trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary objective of this trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared to the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
NCT01986855 ↗	A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2013-12-02	This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The duration of this trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary objective of this trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared to the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
NCT01986881 ↗	Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)	Completed	Pfizer	Phase 3	2013-11-04	An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled). Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.
NCT01986881 ↗	Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2013-11-04	An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled). Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.

Clinical Trial Conditions for Ertugliflozin; Metformin Hydrochloride

Condition Name

Condition Name for Ertugliflozin; Metformin Hydrochloride
Intervention	Trials
Type 2 Diabetes Mellitus	8
Diabetes Mellitus, Type 2	1
Hypertension	1

Condition MeSH

Condition MeSH for Ertugliflozin; Metformin Hydrochloride
Intervention	Trials
Diabetes Mellitus, Type 2	9
Diabetes Mellitus	9
Hypertension	1
Vascular Diseases	1

Clinical Trial Locations for Ertugliflozin; Metformin Hydrochloride

Trials by Country

Trials by Country for Ertugliflozin; Metformin Hydrochloride
Location	Trials
United States	43
Russian Federation	9
Mexico	8
Ukraine	8
Hungary	7

Trials by US State

Trials by US State for Ertugliflozin; Metformin Hydrochloride
Location	Trials
California	3
Illinois	2
Florida	2
Alabama	2
Texas	2

Clinical Trial Progress for Ertugliflozin; Metformin Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Ertugliflozin; Metformin Hydrochloride
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	8

Clinical Trial Status

Clinical Trial Status for Ertugliflozin; Metformin Hydrochloride
Clinical Trial Phase	Trials
Completed	7
Recruiting	1
Withdrawn	1

Clinical Trial Sponsors for Ertugliflozin; Metformin Hydrochloride

Sponsor Name

Sponsor Name for Ertugliflozin; Metformin Hydrochloride
Sponsor	Trials
Merck Sharp & Dohme Corp.	9
Pfizer	8
Cedars-Sinai Medical Center	1

Sponsor Type

Sponsor Type for Ertugliflozin; Metformin Hydrochloride
Sponsor	Trials
Industry	17
Other	1

Ertugliflozin and Metformin Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

Ertugliflozin, marketed under the brand name Steglatro, and its fixed-dose combination (FDC) with metformin hydrochloride, known as Segluromet, are significant advancements in the treatment of type 2 diabetes mellitus (T2DM). This article delves into the clinical trials, market analysis, and future projections for this combination therapy.

Clinical Trials Overview

Efficacy and Safety Studies

Ertugliflozin has been extensively studied in multiple clinical trial settings. Four main studies involving over 3,600 patients with T2DM have demonstrated that adding ertugliflozin to metformin significantly lowers glucose levels, particularly in patients where metformin alone is not sufficient. These studies focused on the effects on HbA1c levels after six months or one year of treatment. The results showed a reduction in HbA1c levels by around 0.8 points compared to metformin alone[1].

Additional Benefits

In addition to glycemic control, these studies revealed that the combination of ertugliflozin and metformin also helps reduce body weight and the risk of heart failure in patients with T2DM[1].

Phase 3 Trials

The efficacy and safety of ertugliflozin were supported by data from four Phase 3 studies (P001/1016, P007/1017, P005/1019, P003/1022) conducted in T2DM patients. These trials evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of ertugliflozin, both as a monotherapy and in combination with other antidiabetic agents like metformin and sitagliptin[3].

Pediatric Studies

Ongoing studies are also investigating the use of ertugliflozin in pediatric patients aged 10 to 17 years, with a focus on pharmacokinetics and exposure-response analysis. These studies aim to determine the appropriate doses of ertugliflozin for this age group[5].

Market Analysis

Cost-Effectiveness

The fixed-dose combination of ertugliflozin and metformin hydrochloride has been shown to be a cost-effective option for payers. A cost-minimization analysis (CMA) demonstrated that this FDC represents the lowest cost option compared to other SGLT2/metformin FDCs and co-administered SGLT2 and metformin. The daily cost savings range from $0.38 to $2.90 compared to individual components[2].

Pricing and Savings

The ertugliflozin plus metformin hydrochloride FDC is priced at parity with ertugliflozin alone, allowing drug plans to benefit from the optimal daily dose of metformin at no additional cost. This results in significant savings due to reduced dispensing fees and lower overall costs[2].

Market Position

While ertugliflozin/metformin FDC is more costly than some second-line therapies like sulfonylureas and thiazolidinediones, it is less costly than other DPP-4 inhibitors and glucagon-like peptide 1 receptor agonists. This positioning makes it a viable option for patients requiring combination therapy[2].

Market Projections

Growing Demand for Combination Therapies

The demand for combination therapies in the management of T2DM is increasing due to the complexity of the disease and the need for comprehensive treatment approaches. Ertugliflozin and metformin hydrochloride FDC is well-positioned to capture a significant share of this market[4].

Expanding Indications

As clinical trials continue to demonstrate the efficacy and safety of ertugliflozin in various patient populations, including those with moderate renal failure and pediatric patients, the market potential for this drug is expected to expand. This could lead to increased adoption and prescription rates[4].

Competitive Landscape

The diabetes market is highly competitive, with several SGLT2 inhibitors and other antidiabetic agents available. However, the unique combination of ertugliflozin and metformin, along with its cost-effectiveness and additional benefits such as weight loss and reduced heart failure risk, gives it a competitive edge[1][2].

Regulatory and Patent Status

Approval and Exclusivity

Ertugliflozin and its FDC with metformin were approved by regulatory bodies in 2017. The exclusivity for both products is based on the ertugliflozin compound patent, which is set to expire in August 2029[3].

Key Takeaways

• Clinical Efficacy: Ertugliflozin and metformin hydrochloride FDC has been shown to effectively lower HbA1c levels, reduce body weight, and decrease the risk of heart failure in patients with T2DM.
• Cost-Effectiveness: This combination therapy is a cost-effective option for payers, offering significant daily cost savings compared to other treatment options.
• Market Position: The drug is well-positioned in the market due to its unique benefits and competitive pricing.
• Future Projections: The demand for combination therapies is expected to grow, and ongoing clinical trials may expand the indications for ertugliflozin.

FAQs

Q: What are the primary indications for ertugliflozin and metformin hydrochloride FDC?

A: The primary indications are for the control of hyperglycemia in adults with type 2 diabetes as an adjunct to diet and exercise, particularly in patients where metformin alone is not sufficient[4].

Q: How does the combination of ertugliflozin and metformin compare in terms of cost?

A: The combination is cost-effective, offering daily cost savings of up to $2.90 compared to co-administered SGLT2 and metformin[2].

Q: What additional benefits does the combination of ertugliflozin and metformin provide?

A: Besides lowering glucose levels, this combination helps reduce body weight and the risk of heart failure in patients with T2DM[1].

Q: Are there ongoing clinical trials for ertugliflozin in pediatric patients?

A: Yes, ongoing studies are investigating the use of ertugliflozin in pediatric patients aged 10 to 17 years, focusing on pharmacokinetics and exposure-response analysis[5].

Q: When does the patent exclusivity for ertugliflozin and its FDC with metformin expire?

A: The patent exclusivity is set to expire in August 2029[3].

Sources

1. European Medicines Agency (EMA). Segluromet | European Medicines Agency (EMA).
2. NCBI Bookshelf. Pharmacoeconomic Evaluation - NCBI Bookshelf - NCBI.
3. FDA. 209803Orig1s000 209805Orig1s000 209806Orig1s000.
4. Clinical Diabetes. Overview of Ertugliflozin | Clinical Diabetes.
5. FDA. center for drug evaluation and research - accessdata.fda.gov.