Investigational Study of Delayed Release Metformin

NCT04854512 | Suspended Phase 3 FDA Drug

• 1 other identifier: ANJ900D3501
• Study Type: interventional
• Target: 675
• Locations: 8 countries
• Sites: 87

Brief Summary

In Phase 1 and 2 studies already conducted, Metformin DR, with its targeted delivery to the distal small intestine, has shown the potential to be a safe and effective way to improve glycemic control in patients with T2DM and CKD with less systemic metformin exposure. The primary purpose of this Phase 3 clinical study is to collect pivotal data confirming the safety and efficacy of Metformin DR in T2DM patients with varying renal function from normal up to CKD3B.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

  Change in HbA1c in patients treated with Metformin DR compared to placebo

  Baseline to 28 weeks

Secondary Outcomes (3)

• HbA1c response (Metformin DR vs. placebo)

  Baseline to 28 weeks

• Change in HbA1c (Met DR vs. metformin IR)

  Baseline to 28 weeks

• HbA1c response (Metformin DR vs. metformin IR)

  Baseline to 28 weeks

Study Arms (3)

Investigational Arm (Metformin DR plus metformin IR placebo)

EXPERIMENTAL

Group A will receive 1800 mg Metformin DR qAM + placebo for 1500 mg metformin IR in divided doses (2×placebo for metformin IR 500 mg qAM and 1×placebo for metformin IR 500 mg qPM).

Drug: Metformin DR; Drug: Metformin IR placebo

Placebo Arm (Metformin DR placebo plus metformin IR placebo)

PLACEBO COMPARATOR

Group B will receive placebo for 1800 mg Metformin DR qAM + placebo for 1500 mg metformin IR in divided doses (2× placebo for metformin IR 500 mg qAM and 1×placebo for metformin IR 500 mg qPM).

Drug: Metformin DR Placebo; Drug: Metformin IR placebo

Active Control Arm (Metformin DR placebo plus metformin IR)

ACTIVE COMPARATOR

Group C will receive placebo for 1800 mg Metformin DR qAM + 1500 mg metformin IR in divided doses (2× metformin IR 500 mg qAM and 1× metformin IR 500 mg qPM).

Drug: Metformin IR; Drug: Metformin DR Placebo

Interventions

Metformin DR DRUG

Delay-Release Metformin

Also known as: ANJ900, MetDR

Investigational Arm (Metformin DR plus metformin IR placebo)

Metformin IR DRUG

Immediate Release Metformin

Active Control Arm (Metformin DR placebo plus metformin IR)

Metformin DR Placebo DRUG

Metformin DR Placebo

Active Control Arm (Metformin DR placebo plus metformin IR); Placebo Arm (Metformin DR placebo plus metformin IR placebo)

Metformin IR placebo DRUG

Metformin IR placebo

Investigational Arm (Metformin DR plus metformin IR placebo); Placebo Arm (Metformin DR placebo plus metformin IR placebo)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is male or female and at least 18 years old
• Has body mass index 20.0 to 45.0 kg/m2 (inclusive)
• Has T2DM
• Has HbA1c of 7.0% to 9.5%, inclusive, at Visit 1A and HbA1c value of 7.0% to 10.5%, inclusive, at Week -2 (Visit 3/3A as applicable)
• Has an eGFR value of ≥30 mL/min/1.73 m2 based on the CKD-EPI equation at Visit 1A and Visit 3/3A (Week -2)
• Stable treatment with a metformin preparation or a combination product containing metformin for 8 weeks prior to Visit 1A
• If treated with the following medications, must be on a stable regimen for a minimum of 6 weeks prior to Visit 1B
• Drugs known to affect body weight, including prescription medications (e.g., phentermine, phentermine/topiramate, orlistat, lorcaserin, bupropion/naltrexone) and over-the-counter anti-obesity agents
• Hormone replacement therapy (female patients) and testosterone (male patients)
• Oral contraceptives (female patients)
• Antihypertensive agents including ACEi/ARB
• Lipid-lowering agents
• Thyroid replacement therapy
• Antidepressant agents
• Ability to understand and willingness to adhere to protocol requirements

You may not qualify if:

• Is currently on dialysis, has been on any dialysis within 1 year of Visit 1B, or is expected to undergo dialysis during the study period
• Has a history of lactic acidosis
• Has a fasting plasma glucose (FPG) value \>240 mg/dL (\>13.3 mmol/L) at Week -2 (Visit 3/3A as applicable)
• An alanine aminotransferase or aspartate aminotransferase result \>2.5 × upper limit of normal (ULN) or a bilirubin result \>1.5 × ULN at Visit 1B or Visit 3/3A (Week -2) (except in case of documented Gilbert's syndrome)
• Has a fasting plasma lactate value \>2 mol at Visit 1B
• Has a bicarbonate value ≤20 mEq/L at both Visit 1A and 1B. If bicarbonate value is \<20 at Visit 3/3A or 4, patient may be excluded if the investigator considers this clinically significant
• A history of \>5% weight change within 12 weeks prior to Visit 1A
• Has mean BP measurements \>180 mmHg (systolic BP) or \>100 mmHg (diastolic BP) at Visit 1A or Visit 3/3A, which can be rechecked within 1 week (Note: re-screening is allowed 6 weeks after initiation/modification of antihypertensive agents if the patient is screen failed due to BP only)
• Oral antidiabetic agent or insulin use that is not stable for 8 weeks prior to randomization (i.e., change in oral medication dose or basal insulin dose increased or decreased by more than 20% during the 8 weeks prior to Visit 4 \[Day 1\])
• Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following excluded medications:
• Prescribed metformin preparation after initiation of metformin washout following Visit 1B
• Planned use of proton pump inhibitors after Visit 2 (Week -6); such use could potentially affect the DR and PK of Metformin DR. Proton pump inhibitor treatment may be replaced by other treatment (such as H2 receptor antagonists \[excluding ranitidine\], or calcium carbonate antacids) prior to Visit 4 (Day 1), if appropriate per the judgment of the Investigator
• Cationic drugs that are eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, flecainide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) within 1 week of Visit 3 (Week 2)
• Iodinated contrast dye within 1 week prior to Visit 3 (Week -2)
• Investigational drug within 8 weeks (or 5 half-lives of the investigational drug, whichever is greater) of the date of the first dose of randomized study medication

Sponsors & Collaborators

• Anji Pharma: lead

Study Sites (87)

Lenzmeier Family Medicine/CCT Research

Glendale, Arizona, 85308, United States

Location

Aventiv Research

Mesa, Arizona, 85210, United States

Location

Kidney & Hypertension Center / DaVita Clinical Research

Apple Valley, California, 92307, United States

Location

California Institute of Renal Research

Chula Vista, California, 91910, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Valley Renal Medical Group Research

Northridge, California, 91324, United States

Location

San Fernando Valley Health Institute

Van Nuys, California, 91405, United States

Location

AGA Clinical Trials

Hialeah, Florida, 33012, United States

Location

East Coast Institutue for Research

Jacksonville, Florida, 32204, United States

Location

East Coast Institute for Research, LLC

Lake City, Florida, 32055, United States

Location

West Orange Endocrinology

Ocoee, Florida, 34761, United States

Location

Metabolic Research Institute, Inc

West Palm Beach, Florida, 33401, United States

Location

Georgia Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

Location

In-Quest Medical Research - Peachtree

Peachtree Corners, Georgia, 30071, United States

Location

Louisville Metabolic and Atherosclerosis Research Center Inc. (L-MARC)

Louisville, Kentucky, 40213, United States

Location

Methodist Physicians Clinic / CCT Research

Fremont, Nebraska, 68025, United States

Location

Midwest Regional Health Services

Omaha, Nebraska, 68144, United States

Location

DaVita Clinical Research

Las Vegas, Nevada, 89128, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Albuquerque Clinical Trials, Inc.

Albuquerque, New Mexico, 87102, United States

Location

Carolina Institute for Clinical Research

Fayetteville, North Carolina, 28303, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

Eastern Nephrology Associates

New Bern, North Carolina, 28562, United States

Location

Family Medicine of SayeBrook

Myrtle Beach, South Carolina, 29579, United States

Location

South Carolina Clinical Research LLC

Orangeburg, South Carolina, 29118, United States

Location

WR-ClinSearch

Chattanooga, Tennessee, 37421, United States

Location

Texas Diabetes & Endocrinology

Austin, Texas, 78731, United States

Location

Office of Osvaldo A Brusco, MD

Corpus Christi, Texas, 78414, United States

Location

Galenos Research

Dallas, Texas, 75251, United States

Location

Endocrine IPS, PLLC

Houston, Texas, 77079, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78212, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

IACT Health

Suffolk, Virginia, 23435, United States

Location

Instituto de Ensino e Pesquisa Clinica do Ceara

Fortaleza, Ceará, 60170-320, Brazil

Location

Centro de Pesquisas em Diabetes e Doencas Endrocrino-Metabolica Ltda

Fortaleza, Ceará, Brazil

Location

Centro de Diabetes Curitiba

Curitiba, Paraná, Brazil

Location

Cline Research Center

Curitiba, Paraná, Brazil

Location

Universidade Federal Do Para (UFPA) - Insitituto de Ciencas de Saude (ICS)

Belém, Pará, Brazil

Location

IBPClin Instituto Brasil de Pesquisa Clinica

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Hospital Sao Vicente de Paulo

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

Centro de Pesquisas em Diabetes Ltda

Porto Alegre, Rio Grande do Sul, Brazil

Location

Loema - Instituto de Pesquisa Clinica

Campinas, São Paulo, 13060-400, Brazil

Location

Instituto de Pesquisa Clinica de Campinas

Campinas, São Paulo, Brazil

Location

ASOMC Endocrinology and Metabolic Diseases

Rousse, 7002, Bulgaria

Location

Medical Cetner Teodora

Rousse, 7003, Bulgaria

Location

Multiprofile Hospital for Active Treatment

Smolyan, 4700, Bulgaria

Location

Fourth Multipfoile Hospital for Active Treatment

Sofia, 1606, Bulgaria

Location

Medical Center New Rehabilition Cetner EOOD

Stara Zagora, 6000, Bulgaria

Location

Diagnostic Culsultative Cetner "Equita" EOOD

Varna, 9000, Bulgaria

Location

Medical Center Leo Clinical EOOD

Varna, 9020, Bulgaria

Location

BC Diabetes

Vancouver, British Columbia, V5Y 3W2, Canada

Location

LMC Manna Research (Barrie)

Barrie, Ontario, L4N 7L3, Canada

Location

LMC Manna Research (Brampton)

Brampton, Ontario, L6S 0C6, Canada

Location

Stephen S. Chow Medicine Professional Corporation

East York, Ontario, M4C 5T2, Canada

Location

LMC Manna Research (Etobicoke)

Etobicoke, Ontario, M9R 4E1, Canada

Location

LMC Manna Research (Ottawa)

Nepean, Ontario, K2J 4A7, Canada

Location

LMC Manna Research (Bayview)

Toronto, Ontario, M4G 3E8, Canada

Location

LMC Manna Research (Montreal)

Montreal, Quebec, H4T 1Z9, Canada

Location

Diahaza s.r.o.

Holešov, 769 01, Czechia

Location

Diabetologicka ambulance

Krnov, 794 01, Czechia

Location

Interni Ambulance

Olomouc, 77900, Czechia

Location

Endodiab s.r.o.

Prague, 104 00, Czechia

Location

Diabet2 s.r.o.

Prague, 110 00, Czechia

Location

Diabetologicka a podiatricka ambulance, Milan Kvapil s.r.o.

Prague, 149 00, Czechia

Location

ResTrial s.r.o.

Prague, 181 00, Czechia

Location

Borbanya Praxis EU Kft

Nyíregyháza, SZ, 4405, Hungary

Location

Lausmed Kft

Baja, 6500, Hungary

Location

Principal SMO Ltd

Baja, 6500, Hungary

Location

DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, 8230, Hungary

Location

Bajscy-Zsilinszky Hospital

Budapest, 1106, Hungary

Location

Magyar Honvedseg Egeszsegugyl Koxpont

Budapest, 1134, Hungary

Location

Borbanya Praxis EU k ft

Debrecen, 4025, Hungary

Location

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, 8900, Hungary

Location

Malopolskie Centrum Kliniczne

Krakow, Lesser Poland Voivodeship, 30-149, Poland

Location

NZOZ NEUROMED M.iM. Nastaj Sp.P.

Lublin, Lublin Voivodeship, 20-064, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno-Diabetologiczny

Bialystok, 15-435, Poland

Location

Centrum Medyczne Pratia

Katowice, 40-081, Poland

Location

Pro Familia Altera Sp. z.o.o.

Katowice, 40-648, Poland

Location

Diamond Medical Center

Krakow, 31-559, Poland

Location

NBR Polska

Warsaw, 00-0465, Poland

Location

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji

Warsaw, 02-507, Poland

Location

Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska, Centrum Badan Klinicznych Osrodek Badan Wczesnej Fazy

Wroclaw, 51-162, Poland

Location

Hospital Universitario Virgen del Rocio

Seville, SE, 41013, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Nuevas Tecnologias en Diabetes y Endocrinologia

Seville, 41003, Spain

Location

Hospital Vithas Sevilla

Seville, 41950, Spain

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Dan Meyers, MD

  Chief Medical Officer - Anji Pharma

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 22, 2021
• Study Start: May 18, 2021
• Primary Completion: December 1, 2023
• Study Completion: June 30, 2024
• Last Updated: March 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BU (7); HU (8); BR (10); US (33); CA (8); CZ (7); ES (5); PL (9)