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DREAM-T2D: Investigational Study of Delayed Release Metformin

Sponsor
Anji Pharma (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04854512
Collaborator
(none)
675
Enrollment
87
Locations
3
Arms
37.4
Anticipated Duration (Months)
7.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Metformin DR
  • Drug: Metformin IR
  • Drug: Metformin DR Placebo
  • Drug: Metformin IR placebo
 Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
675 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Randomized, Multicenter, Double-blind, Parallel-Group, Placebo & Comparator-Controlled Study to Compare the Glycemic Effects, Safety & Tolerability of Metformin Delayed-Release Tablets in Patients With Type 2 Diabetes Mellitus
Actual Study Start Date :
May 18, 2021
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Jun 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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).

Drug: Metformin DR
Delay-Release Metformin
Other Names:
  • ANJ900
  • MetDR

    • Drug: Metformin IR placebo
    Metformin IR placebo
    Placebo Comparator: 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).

    Drug: Metformin DR Placebo
    Metformin DR Placebo

    Drug: Metformin IR placebo
    Metformin IR placebo
    Active Comparator: 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).

    Drug: Metformin IR
    Immediate Release Metformin

    Drug: Metformin DR Placebo
    Metformin DR Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Change in HbA1c [Baseline to 28 weeks]

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

    Secondary Outcome Measures

    1. HbA1c response (Metformin DR vs. placebo) [Baseline to 28 weeks]

      HbA1c absolute value-based response (Yes/No) at Week 28 defined as HbA1c ≤7% for Metformin DR compared to placebo

    2. Change in HbA1c (Met DR vs. metformin IR) [Baseline to 28 weeks]

      Change in HbA1c from the double-blind treatment period baseline to Week 28 for Metformin DR compared to Metformin IR

    3. HbA1c response (Metformin DR vs. metformin IR) [Baseline to 28 weeks]

      HbA1c absolute value-based response (Yes/No) at Week 28 defined as HbA1c ≤7% for Metformin DR compared to Metformin IR.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    8. 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

    9. Hormone replacement therapy (female patients) and testosterone (male patients)

    10. Oral contraceptives (female patients)

    11. Antihypertensive agents including ACEi/ARB

    12. Lipid-lowering agents

    13. Thyroid replacement therapy

    14. Antidepressant agents

    15. 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:

    11. Prescribed metformin preparation after initiation of metformin washout following Visit 1B

    12. 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

    13. 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

    14. 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)

    15. Iodinated contrast dye within 1 week prior to Visit 3 (Week -2)

    16. 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

    17. Metformin DR or double-blind matching placebo for Metformin DR at any time prior to Visit 1B

    18. 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:

    19. Hepatic disease

    20. Gastrointestinal disease, including but not limited to:

    1. 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

    1. 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)

    2. Has a history of diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycemia within 1 year prior to Visit 1B

    3. A physical, psychological, or historical finding that, in the Investigator's opinion, would make the patient unsuitable for the study

    4. 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

    5. 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

    6. 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

    7. Prior or planned major surgery of any kind (requiring overnight hospitalization) within 6 months of Visit 1B

    8. Patients insufficiently compliant with study medication during the placebo run-in phase (<85% or >115%) as assessed at Visit 4

    9. Is screening for the study at more than one clinical site or is participating in any other clinical study

    10. Is currently pregnant (confirmed by serum pregnancy test at Visit 1B) or breastfeeding or plans to become pregnant during the course of the study

    11. 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

    12. 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

    13. Is employed by Anji Pharma (that is an employee, contract worker, or designee of the company).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Lenzmeier Family Medicine/CCT Research Glendale Arizona United States 85308
    2 Aventiv Research Mesa Arizona United States 85210
    3 Kidney & Hypertension Center / DaVita Clinical Research Apple Valley California United States 92307
    4 California Institute of Renal Research Chula Vista California United States 91910
    5 Academic Medical Research Institute Los Angeles California United States 90022
    6 Valley Renal Medical Group Research Northridge California United States 91324
    7 San Fernando Valley Health Institute Van Nuys California United States 91405
    8 AGA Clinical Trials Hialeah Florida United States 33012
    9 East Coast Institutue for Research Jacksonville Florida United States 32204
    10 East Coast Institute for Research, LLC Lake City Florida United States 32055
    11 West Orange Endocrinology Ocoee Florida United States 34761
    12 Metabolic Research Institute, Inc West Palm Beach Florida United States 33401
    13 Georgia Nephrology Research Institute Lawrenceville Georgia United States 30046
    14 In-Quest Medical Research - Peachtree Peachtree Corners Georgia United States 30071
    15 Louisville Metabolic and Atherosclerosis Research Center Inc. (L-MARC) Louisville Kentucky United States 40213
    16 Methodist Physicians Clinic / CCT Research Fremont Nebraska United States 68025
    17 Midwest Regional Health Services Omaha Nebraska United States 68144
    18 DaVita Clinical Research Las Vegas Nevada United States 89128
    19 Hassman Research Institute Berlin New Jersey United States 08009
    20 Albuquerque Clinical Trials, Inc. Albuquerque New Mexico United States 87102
    21 Carolina Institute for Clinical Research Fayetteville North Carolina United States 28303
    22 Lucas Research Morehead City North Carolina United States 28557
    23 Eastern Nephrology Associates New Bern North Carolina United States 28562
    24 Family Medicine of SayeBrook Myrtle Beach South Carolina United States 29579
    25 South Carolina Clinical Research LLC Orangeburg South Carolina United States 29118
    26 WR-ClinSearch Chattanooga Tennessee United States 37421
    27 Texas Diabetes & Endocrinology Austin Texas United States 78731
    28 Office of Osvaldo A Brusco, MD Corpus Christi Texas United States 78414
    29 Galenos Research Dallas Texas United States 75251
    30 Endocrine IPS, PLLC Houston Texas United States 77079
    31 Clinical Advancement Center, PLLC San Antonio Texas United States 78212
    32 Manassas Clinical Research Center Manassas Virginia United States 20110
    33 IACT Health Suffolk Virginia United States 23435
    34 Instituto de Ensino e Pesquisa Clinica do Ceara Fortaleza CE Brazil 60170-320
    35 Centro de Pesquisas em Diabetes e Doencas Endrocrino-Metabolica Ltda Fortaleza CE Brazil
    36 Universidade Federal Do Para (UFPA) - Insitituto de Ciencas de Saude (ICS) Belem PA Brazil
    37 Centro de Diabetes Curitiba Curitiba PR Brazil
    38 Cline Research Center Curitiba PR Brazil
    39 IBPClin Instituto Brasil de Pesquisa Clinica Rio De Janeiro RJ Brazil
    40 Hospital Sao Vicente de Paulo Passo Fundo RS Brazil 99010-080
    41 Centro de Pesquisas em Diabetes Ltda Porto Alegre RS Brazil
    42 Loema - Instituto de Pesquisa Clinica Campinas SP Brazil 13060-400
    43 Instituto de Pesquisa Clinica de Campinas Campinas SP Brazil
    44 ASOMC Endocrinology and Metabolic Diseases Ruse Bulgaria 7002
    45 Medical Cetner Teodora Ruse Bulgaria 7003
    46 Multiprofile Hospital for Active Treatment Smolyan Bulgaria 4700
    47 Fourth Multipfoile Hospital for Active Treatment Sofia Bulgaria 1606
    48 Medical Center New Rehabilition Cetner EOOD Stara Zagora Bulgaria 6000
    49 Diagnostic Culsultative Cetner "Equita" EOOD Varna Bulgaria 9000
    50 Medical Center Leo Clinical EOOD Varna Bulgaria 9020
    51 BC Diabetes Vancouver British Columbia Canada V5Y 3W2
    52 LMC Manna Research (Barrie) Barrie Ontario Canada L4N 7L3
    53 LMC Manna Research (Brampton) Brampton Ontario Canada L6S 0C6
    54 Stephen S. Chow Medicine Professional Corporation East York Ontario Canada M4C 5T2
    55 LMC Manna Research (Etobicoke) Etobicoke Ontario Canada M9R 4E1
    56 LMC Manna Research (Ottawa) Nepean Ontario Canada K2J 4A7
    57 LMC Manna Research (Bayview) Toronto Ontario Canada M4G 3E8
    58 LMC Manna Research (Montreal) Montreal Quebec Canada H4T 1Z9
    59 Diahaza s.r.o. Holešov Czechia 769 01
    60 Diabetologicka ambulance Krnov Czechia 794 01
    61 Interni Ambulance Olomouc Czechia 77900
    62 Endodiab s.r.o. Praha Czechia 104 00
    63 Diabet2 s.r.o. Praha Czechia 110 00
    64 Diabetologicka a podiatricka ambulance, Milan Kvapil s.r.o. Praha Czechia 149 00
    65 ResTrial s.r.o. Praha Czechia 181 00
    66 Borbanya Praxis EU Kft Nyiregyhaza SZ Hungary 4405
    67 Lausmed Kft Baja Hungary 6500
    68 Principal SMO Ltd Baja Hungary 6500
    69 DRC Gyogyszervizsgalo Kozpont Kft Balatonfüred Hungary 8230
    70 Bajscy-Zsilinszky Hospital Budapest Hungary 1106
    71 Magyar Honvedseg Egeszsegugyl Koxpont Budapest Hungary 1134
    72 Borbanya Praxis EU k ft Debrecen Hungary 4025
    73 Zala Megyei Szent Rafael Korhaz Zalaegerszeg Hungary 8900
    74 NZOZ NEUROMED M.iM. Nastaj Sp.P. Lublin LU Poland 20-064
    75 Malopolskie Centrum Kliniczne Kraków MA Poland 30-149
    76 Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno-Diabetologiczny Białystok Poland 15-435
    77 Centrum Medyczne Pratia Katowice Poland 40-081
    78 Pro Familia Altera Sp. z.o.o. Katowice Poland 40-648
    79 Diamond Medical Center Krakow Poland 31-559
    80 NBR Polska Warsaw Poland 00-0465
    81 Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji Warsaw Poland 02-507
    82 Centrum Badan Klinicznych Piotr Napora Lekarze Spolka Partnerska, Centrum Badan Klinicznych Osrodek Badan Wczesnej Fazy Wrocław Poland 51-162
    83 Hospital Universitario Virgen del Rocio Sevilla SE Spain 41013
    84 Hospital Universitario Vall d'Hebron Barcelona Spain 08035
    85 Hospital Universitario Virgen de la Victoria Málaga Spain 29010
    86 Nuevas Tecnologias en Diabetes y Endocrinologia Sevilla Spain 41003
    87 Hospital Vithas Sevilla Sevilla Spain 41950

    Sponsors and Collaborators

    • Anji Pharma

    Investigators

    • Study Chair: Dan Meyers, MD, Chief Medical Officer - Anji Pharma

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Anji Pharma
    ClinicalTrials.gov Identifier:
    NCT04854512
    Other Study ID Numbers:
    • ANJ900D3501
    First Posted:
    Apr 22, 2021
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Metformin

    Study Results

    No Results Posted as of Jun 9, 2022