Metformin Extended Release Versus Metformin Immediate Release in Subjects With Type 2 Diabetes (CONSENT)

CONSENT - Comparison of metfOrmin XR to IR as moNotherapy in the Newly diagnoSed Type 2 diabEtes Patients for the gastroiNtestinal Tolerability and Efficacy: a Randomized, Parallel Control, Open-label and Multicenter Study

This is a Phase 4, prospective, open label, randomized, parallel controlled multicenter trial in which metformin extended release (XR) will be compared with metformin immediate release (IR) for the gastrointestinal tolerability and efficacy in the newly diagnosed subjects with Type 2 diabetes who have glycosylated hemoglobin (HbA1c) value between 7.0 to 10.0 percent (%).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin IR; Drug: Metformin XR

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Darmstadt, Germany
    • Please contact the Merck KGaA Communication Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Diagnosis of Type 2 diabetes mellitus before the screening visit based on the World Health Organization (WHO) diagnostic and classification criteria
• HbA1c value of 7.0-10.0%, inclusive
• Age ranging from 18 to 79 years, inclusive
• Treatment-naive for oral antidiabetic agents (that is, had not received antidiabetic medication previously, or had received antidiabetic medication for at least 14 days and not within 1 month of enrolment)
• Male, or non-pregnant, non-breastfeeding females
• Body mass index (BMI) greater than or equal to (>=) 18.5 and less than (<) 35 kilogram per square meter (kg/m^2)
• In the opinion of the investigator, subjects are well-motivated, capable and willing to continue the study treatment as required during the whole study period, maintain a study dietary, as required for this protocol, attend scheduled visits and be willing to receive phone calls between visits, avoid pregnancy by using an adequate method of contraception throughout the duration of the study for the female subjects of child bearing potential (and if appropriate male subjects with female partners of childbearing potential)
• Written informed consent given before any trial-related activities are carried out

Exclusion criteria:

• Type 1 diabetes
• Previous treatment with insulin or other antidiabetics (including Chinese traditional medicine) for more than 14 days continuously or within 1 month of enrolment
• Any of the protocol-specified cardiovascular conditions within 3 months prior to the screening visit
• Impaired liver function as defined in the protocol
• Serum creatinine values as specified in the protocol
• Known proliferative retinopathy or maculopathy requiring acute treatment, or recurrent major hypoglycemia or hypoglycemic unawareness as judged by the investigator
• Persistent uncontrolled hypertension
• Severe chronic gastrointestinal disease
• Previous history of 1 or more episodes of ketoacidosis or hyperosmolar state/coma
• Currently receiving chronic (>14 days) systemic glucocorticoid therapy (excluding topical, intraocular, inhaled or intranasal preparations) or have received such therapy within 4 weeks of the screening visit
• Current use of beta-blockers, thiazide diuretic, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, nifedipine and isoniazid and cannot be replaced by any other treatment
• Have any hematologic condition that may interfere with HbA1c measurement (for example, hemolytic anemia, sickle-cell disease)
• Have any other condition (such as, known drug or alcohol abuse or a psychiatric disorder) that may prevent the subject from following and completing the protocol
• Known hypersensitivity to Metformin Hydrochloride
• Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Any contraindications to Metformin according to local package insert

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Metformin IR	Drug: Metformin IR; Subjects will receive Metformin Immediate Release (IR) tablets, orally once daily at a dose of 500 milligram (mg) for 1 week, and then dose will increase with increments of 500 mg every week in first 2 weeks to 1500 mg. After that dose will increase up to maximum dose of 2000 mg for the next 2 weeks and will be maintained at 2000 mg until Week 16.; Other Names: Glucophage IR
EXPERIMENTAL: Metformin XR	Drug: Metformin XR; Subjects will receive Metformin Extended Release (XR) tablets, orally once daily at a dose of 500 mg for 1 week, and then dose will increase with increments of 500 mg every week in first 2 weeks to 1500 mg. After that dose will increase up to maximum dose of 2000 mg for the next 2 weeks and will be maintained at 2000 mg until Week 16.; Other Names: Glucophage XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16		Baseline, Week 16
Overall Gastrointestinal (GI) Tolerability Assessed as Percentage of Subjects With Gastrointestinal Adverse Events During Treatment Period	An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.	Baseline up to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Pre-specified Gastrointestinal Adverse Events During Treatment Period	An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects with pre-specified gastrointestinal adverse events (diarrhea, nausea, abdominal pain, bloating, constipation, dyspepsia and flatulence) were reported.	Baseline up to Week 16
Change From Baseline in Fasting Plasma Glucose (FPG) Level at Week 1, 2, 4, 8, 12 and 16		Baseline, Week 1, 2, 4, 8, 12,16
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) Level at Weeks 8 and 16	The 2-hour Postprandial plasma glucose (PPG) level refers to the plasma glucose concentrations after 2 hours of eating.	Baseline, Week 8 and 16
Percentage of Subjects With Hypoglycemia	Hypoglycemia, also called as low blood glucose or low blood sugar, is defined as the blood glucose level of less than normal (that is less than 3.9 millimole per liter [mmol/L]).	Baseline up to Week 16
Percentage of Subjects With Marked Hyperglycemia	Marked hyperglycemia was defined as the FPG level of greater than or equal to 11.1 mmol/L.	Baseline up to Week 16
Percentage of Subjects With HbA1c Less Than (<) 7%		Baseline up to Week 16
Percentage of Subjects Who Are Totally Intolerant to the Treatment	Subjects were considered to be totally intolerant if they experienced a Grade 3 or higher toxicity considered at least possibly related to the treatment.	Baseline up to Week 16
Percentage of Subjects With HbA1c Less Than (<) 7% and With no Severe Gastrointestinal (GI) and Other Adverse Events (AEs)	Percentage of subjects with HbA1c <7% and with no severe GI and other AEs were reported. Severe adverse events were based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 and were defined as those events which were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.	Baseline up to Week 16
Percentage of Subjects Who Are Compliant to Treatment	Compliance was defined as not skipping or forgetting dosing or not delaying the dosing time. Subjects who never missed a dose of medication were considered compliant.	Baseline up to Week 16

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Serono Co., Ltd., Beijing, China

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ACTUAL): November 1, 2015
• Study Completion (ACTUAL): April 1, 2016

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: September 26, 2014
• First Posted (ESTIMATE): September 30, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): January 24, 2017
• Last Update Submitted That Met QC Criteria: November 28, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Diabetes Mellitus, Type 2; Metformin XR; Metformin IR
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 200084-513