A study to assess the efficacy and safety of oral ladarixin given 400 mg twice a day in patients with new-onset type 1 diabetes

Phase 1

Conditions: new onset type 1 diabetes
MedDRA version: 18.0 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 18.0 Level: LLT Classification code 10012608 Term: Diabetes mellitus insulin-dependent System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 18.0 Level: HLT Classification code 10012602 Term: Diabetes mellitus (incl subtypes) System Organ Class: 100000004860
MedDRA version: 18.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 18.0 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2014-003968-20-IT

Lead Sponsor: Dompé farmaceutici s.p.a.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 72

Inclusion Criteria

1.Male and female patients aged 18-45 years, inclusive;
2.New-onset T1D (randomization within 100 days from 1st insulin administration);
3.Positive for at least one diabetes-related auto-antibody (anti-GAD; IAA, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody; ZnT8);
4.Require, or has required at some time, insulin, with the exclusion of patients taking twice daily pre-mixed insulin or on insulin pump;
5.Residual ß-cell function as per peak stimulated (MMTT) C-peptide level >0.6ng/mL (0.2nmol/L); MMTT should not be performed within one week of resolution of a diabetic ketoacidosis event;
6.Patient able to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations;
7.Patients who have given written informed consent prior of any study-related procedure not part of standard medical care;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients taking twice daily pre-mixed insulin or on insulin pump
2.Any other chronic disease, including type 2 diabetes, apart from autoimmune hypothyroidism requiring thyroid hormone replacement only; patients with severe (myxedema) disease potentially requiring immunosuppressive therapy will be excluded;
3.Moderate to severe renal impairment as per calculated creatinine clearance (CLcr) < 60 mL/min according to the Cockcroft-Gault formula (Cockcroft-Gault , 1976);
4.Hepatic dysfunction defined by increased ALT/AST > 3 x upper limit of normal (ULN) and increased total bilirubin > 3 mg/dL [>51.3 µmol/L];
5.Hypoalbuminemia defined as serum albumin < 3 g/dL;
6.QTcF > 470 msec;
7.Complete Left Bundle Branch Block (LBBB), atrio-ventricular block (mobitz II 2nd degree or 2:1 atrio-ventricular block), complete heart block;
8.Electronic pacemaker positioned or implanted defibrillator;
9.History of significant cardiovascular disease;
10.Known hypersensitivity to non-steroidal antiinflammatory drugs;
11.Concomitant treatment with phenytoin, warfarin, sulphanylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (> 50 mg/day);
12.Previous (within 2 weeks prior to randomization) and concomitant treatment with metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin, or any medications known to influence glucose tolerance (e.g. ß-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs, lithium, niacin, etc.);
13.Past (within 1 month prior to randomization) or current administration of any immunosuppressive medications (including oral, inhaled or systemically injected steroids) and use of any investigational agents, including any agents that impact the immune response or the cytokine system;
14.Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this clinical trial is to investigate whether ladarixin has sufficient activity (preservation ofß-cell function and slow-down of the progression of T1D) to warrant its further development (proof of concept trial). ;Secondary Objective: The safety of ladarixin in the specific clinical setting will be also evaluated. ;<br> Primary end point(s): Efficacy endpoint<br> 2-hour area under the curve (AUC) of C-peptide response to a Mixed Meal Tolerance Test (MMTT)<br> ;Timepoint(s) of evaluation of this end point: baseline, week 13±1

Secondary Outcome Measures

Name	Time	Method

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