| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Uncontrolled Type 2 Diabetes Mellitus |
|
| E.1.1.1 | Medical condition in easily understood language |
| Uncontrolled Type 2 Diabetes Mellitus |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067585 |
| E.1.2 | Term | Type 2 diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To describe glycemic control, as measured by HbA1c, in people with T2DM switching from premixed insulins to iGlarLixi using an algorithm based on doses of both insulin components (basal plus mealtime) |
|
| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
1)To establish further clinical benefit of switching from premixed insulins to iGlarLixi, in terms of efficacy.
2)To establish the safety of switching from premixed insulins to iGlarLixi.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each participant must meet all of the following criteria to be enrolled in this study:
1.Is capable of understanding the written informed consent, provides signed written informed consent, is willing and able to complete the electronic diary (eDiary), and agrees to comply with protocol requirements.
2.Is an adult ≥18 years of age.
3.Was diagnosed with T2DM at least 6 months before the screening visit.
4.Has a body mass index (BMI) ≥20 and <40 kg/m² during screening.*
*Body weight and height will be recorded during screening for the calculation of BMI (metric: BMI = weight (kg)/height [m2]).
5.Has an HbA1c ≥7.5% and ≤10.0% during screening.
6.Has fasting plasma glucose (FPG) values before baseline ≥130 mg/dL confirmed by the central laboratory at the screening visit.
7.Has been on premixed insulin therapy (for ≥3 months and <10 years of total duration),* with or without OADs that has to be metformin alone or (metformin, plus sodium-glucose co-transporter-2 (SGLT2) inhibitor or DPP-4i, or SU, all of them , with stable doses for 3 months before the screening visit.
*Allowed premixed combinations include insulin aspart (30%) + insulin aspart protamine (70%); insulin lispro (25%) + insulin lispro protamine (75%); human insulin isophane suspension (70%) and human insulin injection (recombinant DNA origin, 30%); human insulin isophane
suspension (75%) and human insulin injection (recombinant DNA origin,
25%) of >12 units/day and <50 units/day.
8.If female, is not pregnant or breastfeeding and one of the following conditions applies:
8.1) Is a woman of non-childbearing potential (WONCBP), as defined in contraceptive and barrier guidance.
8.2) Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective, with a failure rate of <1%, as described in contraceptive and barrier guidance during the study treatment period (to be effective before starting the intervention) and for at least 1 week after the last administration of study drug.
A WOCBP must have a negative urine pregnancy test at the screening visit.
(Note: If a urine test cannot be confirmed as negative [eg, an ambiguous result], a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.)
9. For participants on daily DPP-4i, willingness to discontinue DPP-4i before switching to iGlarLixi.
10. For participants on SU, willingness to discontinue SU before switching to iGlarLixi. |
|
| E.4 | Principal exclusion criteria |
Participants meeting any of the following criteria will be excluded from the study:
1.Has been diagnosed with type 1 diabetes mellitus (T1DM).
2.Has a history of severe hypoglycemia within 6 months before the screening visit or a history of hypoglycemia unawareness (defined as the onset of neuroglycopenia before the appearance of autonomic warning symptoms or as the failure to sense a significant fall in blood glucose below normal levels).
3.Has been using OADs other than allowed in the inclusion criterion or metformin plus ≥2 OADs within the 3 months before the screening visit.
4.Has a history of discontinuation of a previous treatment with GLP-1 RA due to safety/tolerability reasons or lack of efficacy.
5.Has used weight loss drugs (over-the-counter [OTC] or herbal medications) within 3 months before the screening visit or has a history of bariatric surgery.
6.Has any clinically significant abnormality identified on physical examination, vital sign measurements, or laboratory tests (eg, amylase, lipase, alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3 × upper limit of normal [ULN], calcitonin ≥20 pg/mL) that, in the opinion of the investigator or any qualified designee, would make
implementation of the protocol or interpretation of the study results difficult or would preclude safe participation in the study.
7.Is currently hospitalized (except hospitalization for routine diabetes checkup).
8.Has a history of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, or pancreatectomy.
9.Has severe hypertriglyceridemia (>500 mg/dL).
10.Has clinically relevant history of GI disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis or a history of surgery affecting gastric emptying.
11.Has a history of metabolic acidosis, including diabetic ketoacidosis, within 1 year before the screening visit.
12.Has severe renal impairment or end-stage renal disease, as defined by estimated glomerular filtration rate of <30 mL/min/1.73 m2.
13.Has personal or immediate family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes the participant to MTC (eg, multiple endocrine neoplasia syndromes).
14.Has received systemic glucocorticoid therapy (excluding topical, intra-articular, or ophthalmic application, nasal spray or inhaled forms) for ≥10 consecutive days in the last 3 months before the screening visit.
15.Has current or known history of alcohol or drug abuse within 6 months before the screening visit.
16.Has known presence of factors that interfere with HbA1c measurement (eg, specific hemoglobin variants, hemolytic anemia) that compromises the reliability of HbA1c assessment or has a medical condition that affects interpretation of HbA1c results (eg, blood transfusion or severe blood loss in the last 3 months before the screening visit, any condition that shortens erythrocyte survival).
17.Has contraindications to iGlarLixi in accordance with local label or warning/precaution of use (when appropriate), as displayed in the respective National Product Labeling.
18.Is subject to any country-related specific regulation that would prevent the participant from entering the study.
19.Has been exposed to any investigational drugs in the last 4 weeks or 5 half-lives, whichever is longer, before the screening visit.
20.Is concomitantly enrolled in any other clinical study involving an investigational study drug or any other type of medical research.
21.Is an employee or family member of the investigator or study site personnel.
22.Is currently in an institution because of a regulatory or legal order (ie, is a prisoner or participant who is legally institutionalized).
23.Is not suitable for participation, whatever the reason, as judged by the investigator, including medical or clinical conditions, or potentially is at risk of noncompliance to study procedures.
24.Is involved in a specific situation during study implementation or the course of the study that may raise ethics considerations.
25.Has a hypersensitivity to iGlarLixi, either of its active components (insulin glargine or lixisenatide), or any of its excipients that, in the opinion of the investigator, contraindicates participation in the study.
26. Has previously been treated with combination of insulin degludec and insulin aspart within the 3 months before the screening visit. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in HbA1c from baseline to Week 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1)Percentage of participants achieving a HbA1c target of <7% from baseline to Week 24.
2)Change in total daily insulin dose from baseline to Week 24.
3)Change in fasting plasma glucose (FPG) from baseline to Week 24.
4)Change in PPG at 2 hours after breakfast, derived from 7-point SMPG profile, from baseline to Week 24.
5)Change in average daily blood glucose, derived from 7-point SMPG profile, from baseline to Week 24.
6)Change in body weight from baseline to Week 24.
7)Percentage of participants at HbA1c target of <7% without clinically relevant hypoglycemia, defined as severe hypoglycemia (ADA Level 3) or any hypoglycemia (ADA Level 2) event from baseline to Week 24.
8)Percentage of participants at HbA1c target of <7% without clinically relevant hypoglycemia, defined as severe hypoglycemia (ADA Level 3) or any hypoglycemia (ADA Level 2) event, and without body weight change >0 at Week 24.
9)Hypoglycemia rates during 24 weeks of treatment
9.1)Percentage of participants with at least 1 hypoglycemia event
9.2)Number of events per participant-year
10)Number of participants with AEs and SAEs, including AESIs. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time points for evaluation provided below for corresponding secondary endpoints as numbered in E.5.2 above:
1) Baseline, Week 24
2) Baseline, Week 24
3) Baseline, Week 24
4) Baseline, Week 24
5) Baseline, Week 24
6) Baseline, Week 24
7) Baseline, Week 24
8) Week 24
9.1)Baseline up to Week 24
9.2) Baseline up to Week 24
10) Baseline up to Week 24 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Korea, Republic of |
| Turkey |
| Czechia |
| Poland |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 20 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 27 |
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