Investigational Study of Delayed Release Metformin

NCT ID: NCT04854512

Last Updated: 2023-03-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE3

Total Enrollment

675 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-18

Study Completion Date

2024-06-30

Brief Summary

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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.

Detailed Description

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The study is a multicenter, international study with a 28 week randomized, double blind parallel group, placebo and active comparator controlled period and a 24 week open label extension period in patients with T2DM who are treated with metformin at the time of study screening.

Approximately 675 patients will be randomly assigned to 1 of 3 treatment groups. The study will assess change in HbA1c through 28 weeks for Metformin DR compared to placebo as a primary endpoint. In addition, assessments of change in HbA1c for Metformin DR compared to Metformin IR and assessment of absolute change in HbA1c will be evaluated in the study.

Screening and Run-in Period:

The study will include an up to 10-day screening period, an 4 to 8-week metformin washout period, and a 2-week single blind (patient blinded) placebo run-in period.

Treatment Period:

Patients that are determined eligible based upon the screening and run-in criteria will enter the 28-week double-blind treatment period. During the double-blind treatment period, patients will be randomly assigned to 1 of 3 treatment groups (Group A, B, or C) in a 1:1:1 ratio. The 3 treatments are Metformin DR (1800 mg Metformin DR with matching placebo for Metformin IR), Metformin IR (1500 mg Metformin IR with matching placebo for Metformin DR), and placebo (matching placebo for Metformin IR with matching placebo for Metformin DR). For those patients randomized to Metformin IR, their Metformin IR dose will be titrated to prevent gastrointestinal intolerability:

Open Label Extension Period:

Upon completion of the 28 week treatment patients will be eligible for an additional 24 weeks of open label extension period where assigned study treatment will continue and additional efficacy, safety and tolerability data will be collected and analyzed.

Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Investigational Arm (Metformin DR plus metformin IR placebo)

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).

Group Type EXPERIMENTAL

Metformin DR

Intervention Type DRUG

Delay-Release Metformin

Metformin IR placebo

Intervention Type DRUG

Metformin IR placebo

Placebo Arm (Metformin DR placebo plus metformin IR placebo)

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).

Group Type PLACEBO_COMPARATOR

Metformin DR Placebo

Intervention Type DRUG

Metformin DR Placebo

Metformin IR placebo

Intervention Type DRUG

Metformin IR placebo

Active Control Arm (Metformin DR placebo plus metformin IR)

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).

Group Type ACTIVE_COMPARATOR

Metformin IR

Intervention Type DRUG

Immediate Release Metformin

Metformin DR Placebo

Intervention Type DRUG

Metformin DR Placebo

Interventions

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Metformin DR

Delay-Release Metformin

Intervention Type DRUG

Metformin IR

Immediate Release Metformin

Intervention Type DRUG

Metformin DR Placebo

Metformin DR Placebo

Intervention Type DRUG

Metformin IR placebo

Metformin IR placebo

Intervention Type DRUG

Other Intervention Names

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ANJ900 MetDR

Eligibility Criteria

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Inclusion Criteria

1. Is male or female and at least 18 years old
2. Has body mass index 20.0 to 45.0 kg/m2 (inclusive)
3. Has T2DM
4. 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)
5. 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)
6. Stable treatment with a metformin preparation or a combination product containing metformin for 8 weeks prior to Visit 1A
7. If treated with the following medications, must be on a stable regimen for a minimum of 6 weeks prior to Visit 1B

1. 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
2. Hormone replacement therapy (female patients) and testosterone (male patients)
3. Oral contraceptives (female patients)
4. Antihypertensive agents including ACEi/ARB
5. Lipid-lowering agents
6. Thyroid replacement therapy
7. Antidepressant agents
8. Ability to understand and willingness to adhere to protocol requirements

Exclusion Criteria

1. 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
2. Has a history of lactic acidosis
3. Has a fasting plasma glucose (FPG) value \>240 mg/dL (\>13.3 mmol/L) at Week -2 (Visit 3/3A as applicable)
4. 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)
5. Has a fasting plasma lactate value \>2 mol at Visit 1B
6. 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
7. A history of \>5% weight change within 12 weeks prior to Visit 1A
8. 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)
9. 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 \[Day 1\])
10. Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following excluded medications:

1. Prescribed metformin preparation after initiation of metformin washout following Visit 1B
2. Greater than 10 consecutive days of systemic corticosteroids by oral, intravenous, or intramuscular route within 12 weeks of Visit 1B; inhaled, intranasal, ophthalmic, topical, or intra-articular corticosteroids are not exclusionary
3. 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
4. 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)
5. Iodinated contrast dye within 1 week prior to Visit 3 (Week -2)
6. 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
7. Metformin DR or double-blind matching placebo for Metformin DR at any time prior to Visit 1B
11. Has a clinically significant medical condition as judged by the Investigator that could potentially affect study participation and/or personal well-being, including but not limited to the following conditions:

1. Hepatic disease
2. Gastrointestinal disease, including but not limited to:

i. History or presence of inflammatory bowel disease or other severe gastrointestinal disease, particularly those that may impact gastric emptying, such as gastroparesis and pyloric stenosis ii. Prior or expected surgical gastrointestinal procedure that may impact the gut hormonal response to study medication such as gastric bypass surgery or gastric banding surgery iii. Active diagnosis of pancreatitis c. Endocrine disorder other than T2DM or hypothyroidism on replacement therapy d. Cardiovascular disease, including history of stroke, decompensated heart failure New York Heart Association Class III or IV, myocardial infarction, unstable angina pectoris, or coronary arterial bypass graft or angioplasty within 3 months prior to Visit 1A (screening) e. Central nervous system diseases such as epilepsy f. Psychiatric or neurological disorders that in the Investigator's opinion would cause the patient to be noncompliant with study procedures g. Organ transplantation h. Chronic or acute infection requiring systemic antibiotic treatment i. Orthostatic hypotension or syncope j. Active malignancy within the past 5 years with exception of basal cell and squamous cell carcinoma
12. Known allergy or hypersensitivity to Metformin DR, Metformin IR, or placebo or any inactive component of study medication, active comparator, or placebo, unless the reaction is deemed irrelevant to the study by the Investigator (prior history of gastrointestinal intolerance to metformin is not exclusionary)
13. Has a history of diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycemia within 1 year prior to Visit 1B
14. A physical, psychological, or historical finding that, in the Investigator's opinion, would make the patient unsuitable for the study
15. Any verified clinically significant abnormality identified on physical examination, laboratory tests, ECG, vital signs, or any adverse event (AE) at the time of Visit 1B through Visit 4 that, in the judgment of the Investigator or any Sub-investigator, would preclude safe completion of the study or constrains efficacy assessment
16. Currently abuses drugs or alcohol or has a known history of abuse that in the Investigator's opinion would cause the patient to be noncompliant with study procedures
17. Had a blood transfusion or experienced significant blood loss (i.e., \>500 mL), including loss due to blood donation, within 8 weeks prior to Visit 1B, or is planning to donate blood or have a blood transfusion during the study
18. Prior or planned major surgery of any kind (requiring overnight hospitalization) within 6 months of Visit 1B
19. Patients insufficiently compliant with study medication during the placebo run-in phase (\<85% or \>115%) as assessed at Visit 4
20. Is screening for the study at more than one clinical site or is participating in any other clinical study
21. Is currently pregnant (confirmed by serum pregnancy test at Visit 1B) or breastfeeding or plans to become pregnant during the course of the study
22. Women of childbearing potential not willing to use highly effective method(s) of birth control during the entire study, or who are unwilling or unable to be tested for pregnancy
23. If the patient has evidence of coronavirus disease 2019 (COVID-19) within 2 weeks prior to enrolment (a positive COVID-19 test or suspicion of COVID-19 infection), the patient cannot be enrolled in the study
24. Is employed by Anji Pharma (that is an employee, contract worker, or designee of the company).
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Anji Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dan Meyers, MD

Role: STUDY_CHAIR

Chief Medical Officer - Anji Pharma

Locations

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Lenzmeier Family Medicine/CCT Research

Glendale, Arizona, United States

Site Status

Aventiv Research

Mesa, Arizona, United States

Site Status

Kidney & Hypertension Center / DaVita Clinical Research

Apple Valley, California, United States

Site Status

California Institute of Renal Research

Chula Vista, California, United States

Site Status

Academic Medical Research Institute

Los Angeles, California, United States

Site Status

Valley Renal Medical Group Research

Northridge, California, United States

Site Status

San Fernando Valley Health Institute

Van Nuys, California, United States

Site Status

AGA Clinical Trials

Hialeah, Florida, United States

Site Status

East Coast Institutue for Research

Jacksonville, Florida, United States

Site Status

East Coast Institute for Research, LLC

Lake City, Florida, United States

Site Status

West Orange Endocrinology

Ocoee, Florida, United States

Site Status

Metabolic Research Institute, Inc

West Palm Beach, Florida, United States

Site Status

Georgia Nephrology Research Institute

Lawrenceville, Georgia, United States

Site Status

In-Quest Medical Research - Peachtree

Peachtree Corners, Georgia, United States

Site Status

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

Louisville, Kentucky, United States

Site Status

Methodist Physicians Clinic / CCT Research

Fremont, Nebraska, United States

Site Status

Midwest Regional Health Services

Omaha, Nebraska, United States

Site Status

DaVita Clinical Research

Las Vegas, Nevada, United States

Site Status

Hassman Research Institute

Berlin, New Jersey, United States

Site Status

Albuquerque Clinical Trials, Inc.

Albuquerque, New Mexico, United States

Site Status

Carolina Institute for Clinical Research

Fayetteville, North Carolina, United States

Site Status

Lucas Research

Morehead City, North Carolina, United States

Site Status

Eastern Nephrology Associates

New Bern, North Carolina, United States

Site Status

Family Medicine of SayeBrook

Myrtle Beach, South Carolina, United States

Site Status

South Carolina Clinical Research LLC

Orangeburg, South Carolina, United States

Site Status

WR-ClinSearch

Chattanooga, Tennessee, United States

Site Status

Texas Diabetes & Endocrinology

Austin, Texas, United States

Site Status

Office of Osvaldo A Brusco, MD

Corpus Christi, Texas, United States

Site Status

Galenos Research

Dallas, Texas, United States

Site Status

Endocrine IPS, PLLC

Houston, Texas, United States

Site Status

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

Site Status

Manassas Clinical Research Center

Manassas, Virginia, United States

Site Status

IACT Health

Suffolk, Virginia, United States

Site Status

Instituto de Ensino e Pesquisa Clinica do Ceara

Fortaleza, Ceará, Brazil

Site Status

Centro de Pesquisas em Diabetes e Doencas Endrocrino-Metabolica Ltda

Fortaleza, Ceará, Brazil

Site Status

Centro de Diabetes Curitiba

Curitiba, Paraná, Brazil

Site Status

Cline Research Center

Curitiba, Paraná, Brazil

Site Status

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

Belém, Pará, Brazil

Site Status

IBPClin Instituto Brasil de Pesquisa Clinica

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Hospital Sao Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Site Status

Centro de Pesquisas em Diabetes Ltda

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Loema - Instituto de Pesquisa Clinica

Campinas, São Paulo, Brazil

Site Status

Instituto de Pesquisa Clinica de Campinas

Campinas, São Paulo, Brazil

Site Status

ASOMC Endocrinology and Metabolic Diseases

Rousse, , Bulgaria

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Medical Cetner Teodora

Rousse, , Bulgaria

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Multiprofile Hospital for Active Treatment

Smolyan, , Bulgaria

Site Status

Fourth Multipfoile Hospital for Active Treatment

Sofia, , Bulgaria

Site Status

Medical Center New Rehabilition Cetner EOOD

Stara Zagora, , Bulgaria

Site Status

Diagnostic Culsultative Cetner "Equita" EOOD

Varna, , Bulgaria

Site Status

Medical Center Leo Clinical EOOD

Varna, , Bulgaria

Site Status

BC Diabetes

Vancouver, British Columbia, Canada

Site Status

LMC Manna Research (Barrie)

Barrie, Ontario, Canada

Site Status

LMC Manna Research (Brampton)

Brampton, Ontario, Canada

Site Status

Stephen S. Chow Medicine Professional Corporation

East York, Ontario, Canada

Site Status

LMC Manna Research (Etobicoke)

Etobicoke, Ontario, Canada

Site Status

LMC Manna Research (Ottawa)

Nepean, Ontario, Canada

Site Status

LMC Manna Research (Bayview)

Toronto, Ontario, Canada

Site Status

LMC Manna Research (Montreal)

Montreal, Quebec, Canada

Site Status

Diahaza s.r.o.

Holešov, , Czechia

Site Status

Diabetologicka ambulance

Krnov, , Czechia

Site Status

Interni Ambulance

Olomouc, , Czechia

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Endodiab s.r.o.

Prague, , Czechia

Site Status

Diabet2 s.r.o.

Prague, , Czechia

Site Status

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

Prague, , Czechia

Site Status

ResTrial s.r.o.

Prague, , Czechia

Site Status

Borbanya Praxis EU Kft

Nyíregyháza, SZ, Hungary

Site Status

Lausmed Kft

Baja, , Hungary

Site Status

Principal SMO Ltd

Baja, , Hungary

Site Status

DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, , Hungary

Site Status

Bajscy-Zsilinszky Hospital

Budapest, , Hungary

Site Status

Magyar Honvedseg Egeszsegugyl Koxpont

Budapest, , Hungary

Site Status

Borbanya Praxis EU k ft

Debrecen, , Hungary

Site Status

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, , Hungary

Site Status

Malopolskie Centrum Kliniczne

Krakow, Lesser Poland Voivodeship, Poland

Site Status

NZOZ NEUROMED M.iM. Nastaj Sp.P.

Lublin, Lublin Voivodeship, Poland

Site Status

Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno-Diabetologiczny

Bialystok, , Poland

Site Status

Centrum Medyczne Pratia

Katowice, , Poland

Site Status

Pro Familia Altera Sp. z.o.o.

Katowice, , Poland

Site Status

Diamond Medical Center

Krakow, , Poland

Site Status

NBR Polska

Warsaw, , Poland

Site Status

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji

Warsaw, , Poland

Site Status

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

Wroclaw, , Poland

Site Status

Hospital Universitario Virgen del Rocio

Seville, SE, Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Nuevas Tecnologias en Diabetes y Endocrinologia

Seville, , Spain

Site Status

Hospital Vithas Sevilla

Seville, , Spain

Site Status

Countries

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United States Brazil Bulgaria Canada Czechia Hungary Poland Spain

Other Identifiers

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ANJ900D3501

Identifier Type: -

Identifier Source: org_study_id

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