Type 2 Diabetes Mellitus in Patients who have not Achieved Adequate Glycemic Control with Maximum Tolerated Dose of Metformin Daily or Sulfonylurea MedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: 5- Aminolevulinic acid hydrochloride 50mg Capsules
Pharmaceutical Form: Capsule
CAS Number: 5451-09-2
Current Sponsor code: 5-ALA hydrochloride, ALA hydrochloride,
Other descriptive name
Sponsors
neopharma Japan Co., Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female between 18 and 75 years old (age >18 to =75) at time of informed consent, with a documented diagnosis of T2DM. 2.Written and signed informed consent needs to be provided by patients who are legally capable before starting any protocol-specific procedures. 3.HbA1c between 6.5% and 9% (both inclusive) based on central laboratory results from Visit 1, with individual need for therapy escalation (not to be re-assessed at Randomization Visit 3). 4.Currently treated with a stable MTD of metformin (immediate-release and extended-release) therapy =1500 mg/day or a SU for at least 12 weeks prior to enrolment visit. The patient should remain on therapy with metformin or SU will remain on the same dose for the duration of the study for both treatment arms indicated. 5.Patients willing to follow the CGM procedures. 6.BMI of =40 kg/m2 at Visit 1. 7.C-peptide laboratory value of =1.5 ng/mL (0.495 nmol/L) based on central laboratory results from Visit 1. 8.Female patients of childbearing potential who are sexually active who agree to routinely use adequate contraception from Screening throughout the duration of the study. Women must be one of the following: a.Naturally postmenopausal defined as =1 year without menstruation and =55 years, or b.=65 years) no F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1.Any known complication of T2DM indicating a late disease state 2.History of Type 1 diabetes, maturity onset diabetes of the young, secondary DM or known presence of glutamate decarboxylase 65 antibodies 3.History of diabetic ketoacidosis, hyperosmolar non-ketotic coma, in the 6 months prior to Screening (Visit 1) 4.History of photo-hypersensitivity, porphyria, or hemochromatosis 5.Greater than 5% unexplained weight change during the 3 months prior to enrolment 6.Fasting plasma glucose >270 mg/dL (>15 mmol/L) assessed based on central laboratory results from Visit 1 (can be repeated once during the Screening period) 7.Patients who take acetaminophen containing medications on a regular basis and are unable/unwilling to substitute it the day before placement of the sensor and throughout the 7-day CGM periods 8.History of bariatric surgery or lap-band surgery, or either procedure planned during the time period of the study. History of liposuction is allowed 9.Patients with history of hypersensitivity to porphyrins or history of acute or chronic porphyria 10.History of any unstable endocrine, psychiatric, rapidly progressing or unstable renal disease, or rheumatic disorder 11.Patients who may be at risk for dehydration or volume depletion 12.Has evidence of current abuse of drugs or alcohol or a history of abuse within the past 52 weeks 13.Clinically significant cardiovascular disease or procedure within 3 months prior to Visit 1 or expected to require coronary revascularization procedure during the course of the study 14.Severe uncontrolled arterial hypertension defined as systolic BP =180 mmHg and/or diastolic BP =110 mmHg at any visit up to and including the Randomization visit 15.Presence or history of severe congestive heart failure (Class III and IV) 16.Renal dysfunction with creatinine clearance 3 × upper limit of normal based on central laboratory results from Visit 1 19.Serum total bilirubin of >2.4 mg/dL (?41 mmol/L) (patients with documented Gilbert’s syndrome will be allowed to enroll) based on central laboratory results from Visit 1 20.History of severe hepatobiliary disease or hepatotoxicity with any medication 21.History or serologic evidence of infectious liver disease (Hepatitis B viral antibody IgM, Hepatitis B virus surface antigen and Hepatitis C virus antibody) 22.Any history within 5 years of Visit 1 of any malignancy, with the exception of treated in situ basal cell or squamous cell carcinoma of the skin 23.Hemoglobin <10 g/dL (<100 g/L) or 6.2 mmol/L for men; Hb <9.0 g/dL (<90 g/L) or 5.9 mmol/L for women 24.History of chronic hemolytic anemia or hemoglobinopathies 25.Donation or transfusion of blood, plasma, or platelets within the past 12 weeks prior to enrolment, or planning to donate blood during the study 26.In need of insulin treatment or having received insulin within 12 weeks before Visit 1 with the exception of short-term, acute insulin use for a period less than 7 days total 27.Administration of any anti hyperglycemic therapy, other than metformin or SU, during the 12 weeks prior to Visit 1. Exception for short-term insulin use (?7 days total) during the 9 weeks prior to Visit 1 28.Administration of any other investi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the change from Baseline in Glycated hemoglobin (HbA1c) up to Week 24 between 5 aminolevulinic acid/sodium ferrous citrate (5 ALA/SFC) plus metformin (or sulfonylurea [SU]) and placebo plus metformin (or SU).;Secondary Objective: •To compare the occurrence of hypoglycemic episodes during the Treatment period between the 2-treatment arms •To compare the change from Baseline in total body weight at Week 24 between the 2 arms •To evaluate fructosamine as an alternative biomarker for glycemic control •To explore glucose patterns of 5-ALA/SFC over the 24-hour period during 7 days at Baseline, Week 12 and Week 24, as captured through continuous glucose monitoring for the 2 arms •To compare the need for rescue therapy of 5ALA/SFC plus metformin or SU with placebo plus metformin or SU •To compare additional effects of 5-ALA/SFC plus metformin or SU with placebo plus metformin or SU at Week 24 •To explore the change from Baseline in laboratory assessments (hemoglobin, total bilirubin, and serum iron/ ferritin/unsaturated iron binding capacity/total iron binding capacity) •To evaluate safety and tolerability of 5-ALA/SFC (adverse events, safety laboratory tests, Self-monitoring of blood glucose and ECG) ;Primary end point(s): Mean change from Baseline in HbA1c to Week 24.;Timepoint(s) of evaluation of this end point: This endpoint will be evaluated at sreening, at baseline (Week 0), Week 4, 8, 12, 20 and Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Slope of change from Baseline in HbA1c from Baseline to Week 24. •Achieving target HbA1c of 6.5% without significant hypoglycemia. •Occurrence of least 1 episode of documented, symptomatic hypoglycemia during the 24 weeks Treatment period. •Occurrence of at least 1 severe hypoglycemic event (2017 American Diabetes Association [ADA] classification) during the 24 weeks Treatment period. •Occurrence of at least 1 episode of documented, symptomatic hypoglycemia during the 24 weeks Treatment period, in the age groups below 65 years and 65 years and older (18 to 64 years; 65 to 75 years). •Achieving HbA1c of =7% and =6.5% without documented, symptomatic hypoglycemia at Week 24. •Achieving HbA1c of =7% and =6.5% at Week 24. •Achieving an HbA1c decrease of =1% with no weight gain at Week 24. •Time spent at or below HbA1c target (=7% and =6.5%) during the 24-weeks Treatment period. •Change in fructosamine levels between Baseline and Week 24. •Change in fructosamine levels at 2 weekly intervals from Baseline until end of study. •Change in Hb, total bilirubin, and serum ferritin over the 24 weeks Treatment period. •Change in body mass index (BMI) from Baseline to Week 24. •Change in waist circumference from Baseline to Week 24. •Achieving weight reduction of =5% or weight gain of =5% from Baseline to Week 24. •Change in BP from Baseline to Week 24. •Requiring rescue therapy for lack of glycemic control in the 2- treatment arms. •Change in average CGM-measured blood glucose (CGMG) from Baseline to Week 12 and Week 24. •Percent (%) of time in different CGM glucose ranges. •Further CGM parameters (Area under curve [AUC], variability parameters). Safety endpoints: •Proportion of patients withdrawing from study due to hypoglycemia. •AEs/ serious adverse events (SAEs). •Adverse event of special interest. •Clinical laboratory tests. •ECG. •Vital signs (pulse and BP). •Body temperature. •Hypoglycemic events. •SMGB. •Physical examinations. ;Timepoint(s) of ev | — |
Countries
Hungary, Poland, Ukraine
Contacts
Public ContactClinical Trial Information Desk
neopharma Japan Co., Ltd.
Outcome results
None listed