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Clinical Trial Details — Status: Suspended

Administrative data

NCT number NCT04854512
Other study ID # ANJ900D3501
Secondary ID
Status Suspended
Phase Phase 3
First received
Last updated
Start date May 18, 2021
Est. completion date June 30, 2024

Study information

Verified date March 2023
Source Anji Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Suspended
Enrollment 675
Est. completion date June 30, 2024
Est. primary completion date December 1, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility 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).

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Metformin DR
Delay-Release Metformin
Metformin IR
Immediate Release Metformin
Metformin DR Placebo
Metformin DR Placebo
Metformin IR placebo
Metformin IR placebo

Locations

Country Name City State
Brazil Universidade Federal Do Para (UFPA) - Insitituto de Ciencas de Saude (ICS) Belem PA
Brazil Instituto de Pesquisa Clinica de Campinas Campinas SP
Brazil Loema - Instituto de Pesquisa Clinica Campinas SP
Brazil Centro de Diabetes Curitiba Curitiba PR
Brazil Cline Research Center Curitiba PR
Brazil Centro de Pesquisas em Diabetes e Doencas Endrocrino-Metabolica Ltda Fortaleza CE
Brazil Instituto de Ensino e Pesquisa Clinica do Ceara Fortaleza CE
Brazil Hospital Sao Vicente de Paulo Passo Fundo RS
Brazil Centro de Pesquisas em Diabetes Ltda Porto Alegre RS
Brazil IBPClin Instituto Brasil de Pesquisa Clinica Rio De Janeiro RJ
Bulgaria ASOMC Endocrinology and Metabolic Diseases Ruse
Bulgaria Medical Cetner Teodora Ruse
Bulgaria Multiprofile Hospital for Active Treatment Smolyan
Bulgaria Fourth Multipfoile Hospital for Active Treatment Sofia
Bulgaria Medical Center New Rehabilition Cetner EOOD Stara Zagora
Bulgaria Diagnostic Culsultative Cetner "Equita" EOOD Varna
Bulgaria Medical Center Leo Clinical EOOD Varna
Canada LMC Manna Research (Barrie) Barrie Ontario
Canada LMC Manna Research (Brampton) Brampton Ontario
Canada Stephen S. Chow Medicine Professional Corporation East York Ontario
Canada LMC Manna Research (Etobicoke) Etobicoke Ontario
Canada LMC Manna Research (Montreal) Montreal Quebec
Canada LMC Manna Research (Ottawa) Nepean Ontario
Canada LMC Manna Research (Bayview) Toronto Ontario
Canada BC Diabetes Vancouver British Columbia
Czechia Diahaza s.r.o. Holešov
Czechia Diabetologicka ambulance Krnov
Czechia Interni Ambulance Olomouc
Czechia Diabet2 s.r.o. Praha
Czechia Diabetologicka a podiatricka ambulance, Milan Kvapil s.r.o. Praha
Czechia Endodiab s.r.o. Praha
Czechia ResTrial s.r.o. Praha
Hungary Lausmed Kft Baja
Hungary Principal SMO Ltd Baja
Hungary DRC Gyogyszervizsgalo Kozpont Kft Balatonfüred
Hungary Bajscy-Zsilinszky Hospital Budapest
Hungary Magyar Honvedseg Egeszsegugyl Koxpont Budapest
Hungary Borbanya Praxis EU k ft Debrecen
Hungary Borbanya Praxis EU Kft Nyiregyhaza SZ
Hungary Zala Megyei Szent Rafael Korhaz Zalaegerszeg
Poland Niepubliczny Zaklad Opieki Zdrowotnej Specjalistyczny Osrodek Internistyczno-Diabetologiczny Bialystok
Poland Centrum Medyczne Pratia Katowice
Poland Pro Familia Altera Sp. z.o.o. Katowice
Poland Diamond Medical Center Krakow
Poland Malopolskie Centrum Kliniczne Kraków MA
Poland NZOZ NEUROMED M.iM. Nastaj Sp.P. Lublin LU
Poland Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji Warsaw
Poland NBR Polska Warsaw
Poland Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska, Centrum Badan Klinicznych Osrodek Badan Wczesnej Fazy Wroclaw
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Hospital Universitario Virgen de la Victoria Málaga
Spain Hospital Universitario Virgen del Rocio Sevilla SE
Spain Hospital Vithas Sevilla Sevilla
Spain Nuevas Tecnologias en Diabetes y Endocrinologia Sevilla
United States Albuquerque Clinical Trials, Inc. Albuquerque New Mexico
United States Kidney & Hypertension Center / DaVita Clinical Research Apple Valley California
United States Texas Diabetes & Endocrinology Austin Texas
United States Hassman Research Institute Berlin New Jersey
United States WR-ClinSearch Chattanooga Tennessee
United States California Institute of Renal Research Chula Vista California
United States Office of Osvaldo A Brusco, MD Corpus Christi Texas
United States Galenos Research Dallas Texas
United States Carolina Institute for Clinical Research Fayetteville North Carolina
United States Methodist Physicians Clinic / CCT Research Fremont Nebraska
United States Lenzmeier Family Medicine/CCT Research Glendale Arizona
United States AGA Clinical Trials Hialeah Florida
United States Endocrine IPS, PLLC Houston Texas
United States East Coast Institutue for Research Jacksonville Florida
United States East Coast Institute for Research, LLC Lake City Florida
United States DaVita Clinical Research Las Vegas Nevada
United States Georgia Nephrology Research Institute Lawrenceville Georgia
United States Academic Medical Research Institute Los Angeles California
United States Louisville Metabolic and Atherosclerosis Research Center Inc. (L-MARC) Louisville Kentucky
United States Manassas Clinical Research Center Manassas Virginia
United States Aventiv Research Mesa Arizona
United States Lucas Research Morehead City North Carolina
United States Family Medicine of SayeBrook Myrtle Beach South Carolina
United States Eastern Nephrology Associates New Bern North Carolina
United States Valley Renal Medical Group Research Northridge California
United States West Orange Endocrinology Ocoee Florida
United States Midwest Regional Health Services Omaha Nebraska
United States South Carolina Clinical Research LLC Orangeburg South Carolina
United States In-Quest Medical Research - Peachtree Peachtree Corners Georgia
United States Clinical Advancement Center, PLLC San Antonio Texas
United States IACT Health Suffolk Virginia
United States San Fernando Valley Health Institute Van Nuys California
United States Metabolic Research Institute, Inc West Palm Beach Florida

Sponsors (1)

Lead Sponsor Collaborator
Anji Pharma

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Canada,  Czechia,  Hungary,  Poland,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in HbA1c Change in HbA1c in patients treated with Metformin DR compared to placebo Baseline to 28 weeks
Secondary HbA1c response (Metformin DR vs. placebo) HbA1c absolute value-based response (Yes/No) at Week 28 defined as HbA1c =7% for Metformin DR compared to placebo Baseline to 28 weeks
Secondary Change in HbA1c (Met DR vs. metformin IR) Change in HbA1c from the double-blind treatment period baseline to Week 28 for Metformin DR compared to Metformin IR Baseline to 28 weeks
Secondary HbA1c response (Metformin DR vs. metformin IR) HbA1c absolute value-based response (Yes/No) at Week 28 defined as HbA1c =7% for Metformin DR compared to Metformin IR. Baseline to 28 weeks
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