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A Phase 2, Multicentre, Randomized, Double-blind, Placebo-controlled Study in Patients With New-onset Type 1 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02814838
Recruitment Status : Completed
First Posted : June 28, 2016
Results First Posted : January 12, 2021
Last Update Posted : January 12, 2021
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Insulin-Dependent
Interventions Drug: Ladarixin
Drug: Placebo
Enrollment 76
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Period Title: Overall Study
Started 50 26
Completed 48 25
Not Completed 2 1
Reason Not Completed
3 agreed dates for the final visit missed             1             0
Consent withdrawal             1             1
Arm/Group Title Ladarixin Placebo Total
Hide Arm/Group Description

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Total of all reporting groups
Overall Number of Baseline Participants 50 26 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
50
 100.0%
26
 100.0%
76
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
Female
21
  42.0%
10
  38.5%
31
  40.8%
Male
29
  58.0%
16
  61.5%
45
  59.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.0%
0
   0.0%
1
   1.3%
White
49
  98.0%
26
 100.0%
75
  98.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
Belgium 20 11 31
Italy 17 10 27
Germany 13 5 18
1.Primary Outcome
Title Area Under the Curve (AUC)(0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Week 13
Hide Description

C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2.

Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of >200mg/dL or <70mg/dL.

After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at week 13+/-1 The 2-hour C-peptide AUC after the MMTT at Week 13±1 was transformed as log(x+1) values.

Time Frame week 13±1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo)
Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 49 26
Mean (Standard Deviation)
Unit of Measure: log(ng*hr/ml [0-2 h]+1)
4.026  (0.4852) 3.886  (0.7446)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Transformed AUC was analyzed with Student t-test for unpaired data using PROC TTEST within SAS® to compare Ladarixin and placebo groups. The estimated treatment difference between Ladarixin and placebo was also presented together with the corresponding 95% confidence interval.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3303
Comments [Not Specified]
Method Student's t test for unpaired samples
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.14 to 0.42
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Area Under the Curve (AUC) (0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Weeks 26 and 52
Hide Description

C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2.

Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of >200mg/dL or <70mg/dL. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at week 13+/-1.

The 2-hour C-peptide AUC after the MMTT at Week 13±1 was transformed as log(x+1) values.

Time Frame Follow-ups at Weeks 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 47 25
Mean (Standard Deviation)
Unit of Measure: log(ng*hr/ml [0-2 h]+1)
FU week 26 Number Analyzed 47 participants 25 participants
3.9351  (0.51710) 3.8076  (0.76473)
FU week 52 Number Analyzed 46 participants 25 participants
3.6371  (0.75222) 3.6380  (0.81268)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at FUP week 26
Type of Statistical Test Superiority
Comments The comparisons between groups on 2-hour AUC C-peptide efficacy endpoint was carried-out using a mixed linear model where the log(x+1) transformed 2-hour AUC C-peptide was the dependent variable, while treatment group, visit, treatment by visit interaction were the fixed factors of the model and patient will be the random effect. An unstructured covariance matrix for each patient is considered and the Kenward-Roger adjustment is used for the degrees of freedom.
Statistical Test of Hypothesis P-Value 0.517
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 0.0984
Confidence Interval (2-Sided) 95%
-0.2028 to 0.3995
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At FUP week 52
Type of Statistical Test Superiority
Comments The comparisons between groups on 2-hour AUC C-peptide efficacy endpoint was carried-out using a mixed linear model where the log(x+1) transformed 2-hour AUC C-peptide was the dependent variable, while treatment group, visit, treatment by visit interaction were the fixed factors of the model and patient will be the random effect. An unstructured covariance matrix for each patient is considered and the Kenward-Roger adjustment is used for the degrees of freedom.
Statistical Test of Hypothesis P-Value 0.7999
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.0486
Confidence Interval (2-Sided) 95%
-0.4294 to 0.3322
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT
Hide Description

C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2.

Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of >200mg/dL or <70mg/dL.

The test was initiated before 10 a.m. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink (Nestlé Nutrition) up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15±5, 30±5, 60±10, 90±10, 120±15, 180±15 min after the meal.

Time Frame Follow-ups at Weeks 13±1, 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 49 25
Mean (Standard Deviation)
Unit of Measure: percentage of change
FU week 13 Number Analyzed 49 participants 25 participants
5.7818  (36.74477) -6.0734  (38.22179)
FU week 26 Number Analyzed 47 participants 24 participants
-0.8701  (42.93044) -13.7347  (37.41900)
FU week 52 Number Analyzed 46 participants 24 participants
-22.2532  (38.84672) -24.2215  (42.67277)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 13
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2224
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 12.0411
Confidence Interval (2-Sided) 95%
-7.3823 to 31.4644
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 26
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3931
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 8.4803
Confidence Interval (2-Sided) 95%
-11.0935 to 28.0541
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7664
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -2.9502
Confidence Interval (2-Sided) 95%
-22.5476 to 16.6473
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Screening in Average (Previous 3 Days) Insulin Requirement
Hide Description

Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded in the interval from randomization to Week 13±1, Week 13±1 to Week 26±2, and Week 26±2 to Week 52±2.

From enrolment, patients were admitted to intensive diabetes management, according to current ADA recommendation [2014]. Patients were instructed to self-monitor their glucose values at least 4 times a day and to report (glucose meter/log) outcome to the diabetes management team. Insulin intake was adjusted to target HbA1c levels of less than 7% and self-monitored (fingerstick):

  • pre-prandial blood glucose of 70-130 mg/dL
  • post-prandial blood glucose < 180 mg/dL
  • bed-time blood glucose of 110-150 mg/dL Telephone calls (outside scheduled visits) were scheduled on a regular basis to ensure optimization of metabolic control.
Time Frame Follow-ups at Weeks 13±1, 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 47 26
Mean (Standard Deviation)
Unit of Measure: IU/kg/day
FU week 13 Number Analyzed 47 participants 26 participants
-0.067  (0.1774) -0.018  (0.1314)
FU week 26 Number Analyzed 47 participants 25 participants
-0.011  (0.2625) 0.032  (0.1699)
FU week 52 Number Analyzed 46 participants 25 participants
0.025  (0.2507) 0.101  (0.2411)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 13
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with Daily Insulin Requirement (IU/kg/day) as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.2225
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.048
Confidence Interval (2-Sided) 95%
-0.1257 to 0.0298
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 26
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with Daily Insulin Requirement (IU/kg/day) as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.551
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.0369
Confidence Interval (2-Sided) 95%
-0.1596 to 0.0858
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 52
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with Daily Insulin Requirement (IU/kg/day) as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.2501
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.063
Confidence Interval (2-Sided) 95%
-0.1712 to 0.0453
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Screening in Glycated Haemoglobin (HbA1c) Levels
Hide Description

HbA1c measurement can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement.

An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests.

Time Frame Follow-ups at Weeks 13±1, 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 48 25
Mean (Standard Deviation)
Unit of Measure: percentage of glycated haemoglobin
FU week 13 Number Analyzed 48 participants 25 participants
-1.40  (1.674) -1.18  (1.352)
FU week 26 Number Analyzed 47 participants 24 participants
-1.19  (2.003) -0.63  (1.141)
FU week 52 Number Analyzed 46 participants 25 participants
-0.69  (2.225) -0.76  (1.333)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at FU week 13
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with HbA1c (%) as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.6252
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.1494
Confidence Interval (2-Sided) 95%
-0.7514 to 0.4526
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At FU week 26
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with HbA1c (%) as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.366
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.2804
Confidence Interval (2-Sided) 95%
-0.8904 to 0.3297
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At FU week 52
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with HbA1c (%) as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.5026
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.2063
Confidence Interval (2-Sided) 95%
-0.3992 to 0.8118
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT
Hide Description Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively; Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below.
Time Frame Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 50 26
Mean (Standard Deviation)
Unit of Measure: nmol/L
Screening - Basal average Number Analyzed 50 participants 26 participants
0.218  (0.1087) 0.225  (0.1416)
Screening - 15 min Number Analyzed 50 participants 26 participants
0.294  (0.1621) 0.299  (0.1779)
Screening - 30 min Number Analyzed 50 participants 26 participants
0.422  (0.2126) 0.452  (0.3036)
Screening - 60 min Number Analyzed 50 participants 25 participants
0.545  (0.2631) 0.537  (0.2354)
Screening - 90 min Number Analyzed 50 participants 25 participants
0.613  (0.2467) 0.581  (0.2486)
Screening - 120 min Number Analyzed 49 participants 26 participants
0.620  (0.2559) 0.656  (0.2923)
Screening - 180 min Number Analyzed 49 participants 25 participants
0.527  (0.2252) 0.550  (0.2277)
week 13 - Basal average Number Analyzed 49 participants 26 participants
0.231  (0.1136) 0.210  (0.1315)
week 13 - 15 min Number Analyzed 49 participants 26 participants
0.300  (0.1385) 0.285  (0.1956)
week 13 - 30 min Number Analyzed 49 participants 26 participants
0.427  (0.2048) 0.392  (0.2418)
week 13 - 60 min Number Analyzed 49 participants 26 participants
0.571  (0.2660) 0.523  (0.2729)
week 13 - 90 min Number Analyzed 49 participants 26 participants
0.620  (0.2859) 0.594  (0.3176)
week 13 - 120 min Number Analyzed 49 participants 26 participants
0.637  (0.2869) 0.601  (0.3050)
week 13 - 180 min Number Analyzed 48 participants 26 participants
0.518  (0.2302) 0.527  (0.2778)
week 26 - Basal average Number Analyzed 47 participants 25 participants
0.212  (0.0941) 0.207  (0.1192)
week 26 - 15 min Number Analyzed 47 participants 25 participants
0.278  (0.1294) 0.260  (0.1426)
week 26 - 30 min Number Analyzed 47 participants 25 participants
0.391  (0.1857) 0.368  (0.2150)
week 26 - 60 min Number Analyzed 47 participants 25 participants
0.534  (0.2463) 0.511  (0.2967)
week 26 - 90 min Number Analyzed 47 participants 25 participants
0.569  (0.2606) 0.552  (0.3101)
week 26 - 120 min Number Analyzed 46 participants 25 participants
0.592  (0.2703) 0.552  (0.2907)
week 26 - 180 min Number Analyzed 47 participants 25 participants
0.504  (0.2189) 0.466  (0.2362)
week 52 - Basal average Number Analyzed 46 participants 25 participants
0.168  (0.1070) 0.178  (0.1068)
week 52 - 15 min Number Analyzed 46 participants 25 participants
0.228  (0.1606) 0.249  (0.1616)
week 52 - 30 min Number Analyzed 46 participants 25 participants
0.321  (0.2231) 0.314  (0.1826)
week 52 - 60 min Number Analyzed 46 participants 25 participants
0.430  (0.2693) 0.440  (0.2671)
week 52 - 90 min Number Analyzed 46 participants 25 participants
0.463  (0.2806) 0.465  (0.2881)
week 52 - 120 min Number Analyzed 46 participants 25 participants
0.503  (0.3085) 0.492  (0.2717)
week 52 - 180 min Number Analyzed 46 participants 25 participants
0.426  (0.2341) 0.443  (0.2441)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 13
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with C-peptide (nmol/L) actual value as dependent variable, treatment, visit, time, treatment by visit interaction, time by visit interaction, treatment by visit by time interaction as fixed effects and time by visit interaction is specified in repeated statement.
Statistical Test of Hypothesis P-Value 0.2527
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 0.0242
Confidence Interval (2-Sided) 95%
-0.0174 to 0.0658
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 26
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with C-peptide (nmol/L) actual value as dependent variable, treatment, visit, time, treatment by visit interaction, time by visit interaction, treatment by visit by time interaction as fixed effects and time by visit interaction is specified in repeated statement.
Statistical Test of Hypothesis P-Value 0.2743
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 0.0236
Confidence Interval (2-Sided) 95%
-0.0188 to 0.066
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 52
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with C-peptide (nmol/L) actual value as dependent variable, treatment, visit, time, treatment by visit interaction, time by visit interaction, treatment by visit by time interaction as fixed effects and time by visit interaction is specified in repeated statement.
Statistical Test of Hypothesis P-Value 0.7856
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.0059
Confidence Interval (2-Sided) 95%
-0.0485 to 0.0367
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT
Hide Description Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively). Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below.
Time Frame Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 50 26
Mean (Standard Deviation)
Unit of Measure: mmol/L
Screening - basal average Number Analyzed 50 participants 26 participants
6.965  (1.6858) 6.855  (1.9507)
Screening - 15 min Number Analyzed 50 participants 26 participants
8.108  (1.8453) 8.013  (2.0941)
Screening - 30 min Number Analyzed 50 participants 26 participants
10.438  (2.2282) 10.096  (2.4694)
Screening - 60 min Number Analyzed 50 participants 25 participants
12.146  (2.9387) 12.068  (2.9204)
Screening - 90 min Number Analyzed 50 participants 25 participants
12.350  (3.4122) 12.076  (3.9156)
Screening - 120 min Number Analyzed 50 participants 26 participants
11.400  (3.4561) 11.827  (4.0204)
Screening - 180 min Number Analyzed 49 participants 25 participants
9.478  (3.6320) 9.652  (4.0549)
Week 13 - Basal average Number Analyzed 49 participants 25 participants
7.074  (1.9973) 6.644  (2.1145)
Week 13 - 15 min Number Analyzed 49 participants 25 participants
8.231  (2.1415) 7.836  (2.2409)
Week 13 - 30 min Number Analyzed 49 participants 25 participants
10.727  (2.5691) 10.224  (2.3600)
Week 13 - 60 min Number Analyzed 49 participants 24 participants
12.614  (3.1536) 12.871  (2.6908)
Week 13 - 90 min Number Analyzed 49 participants 25 participants
12.553  (3.7998) 13.092  (3.1608)
Week 13 - 120 min Number Analyzed 49 participants 25 participants
11.773  (4.0990) 12.260  (3.7590)
Week 13 - 180 min Number Analyzed 49 participants 25 participants
9.761  (3.9834) 9.984  (3.8597)
Week 26 - Basal average Number Analyzed 48 participants 25 participants
7.496  (2.0261) 7.600  (2.6387)
Week 26 - 15 min Number Analyzed 48 participants 24 participants
8.750  (2.0827) 9.058  (2.7026)
Week 26 - 30 min Number Analyzed 48 participants 25 participants
10.927  (2.3901) 11.240  (2.6187)
Week 26 - 60 min Number Analyzed 48 participants 25 participants
13.494  (2.8623) 14.222  (2.8795)
Week 26 - 90 min Number Analyzed 48 participants 25 participants
13.665  (3.8399) 15.020  (3.4469)
Week 26 - 120 min Number Analyzed 48 participants 25 participants
13.240  (4.1302) 14.424  (3.7761)
Week 26 - 180 min Number Analyzed 48 participants 25 participants
10.956  (4.2031) 12.028  (3.8832)
Week 52 - Basal average Number Analyzed 46 participants 25 participants
7.457  (2.3045) 8.163  (2.2251)
Week 52 - 15 min Number Analyzed 46 participants 25 participants
8.939  (2.7210) 9.544  (2.2230)
Week 52 - 30 min Number Analyzed 46 participants 25 participants
11.374  (2.6806) 11.688  (2.6411)
Week 52 - 60 min Number Analyzed 46 participants 24 participants
14.315  (3.1205) 14.725  (2.9631)
Week 52 - 90 min Number Analyzed 46 participants 25 participants
14.911  (3.5768) 15.276  (3.7144)
Week 52 - 120 min Number Analyzed 46 participants 25 participants
14.354  (3.9162) 15.140  (3.7514)
Week 52 - 180 min Number Analyzed 46 participants 25 participants
12.148  (4.0817) 13.148  (3.9136)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 13
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with Glucose (mmol/L) actual value as dependent variable, treatment, visit, time, treatment by visit interaction, time by visit interaction, treatment by visit by time interaction as fixed effects and time by visit interaction is specified in repeated statement.
Statistical Test of Hypothesis P-Value 0.9307
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.0253
Confidence Interval (2-Sided) 95%
-0.5986 to 0.548
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 26
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with Glucose (mmol/L) actual value as dependent variable, treatment, visit, time, treatment by visit interaction, time by visit interaction, treatment by visit by time interaction as fixed effects and time by visit interaction is specified in repeated statement.
Statistical Test of Hypothesis P-Value 0.0139
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.7236
Confidence Interval (2-Sided) 95%
-1.2989 to -0.1483
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 52
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with Glucose (mmol/L) actual value as dependent variable, treatment, visit, time, treatment by visit interaction, time by visit interaction, treatment by visit by time interaction as fixed effects and time by visit interaction is specified in repeated statement.
Statistical Test of Hypothesis P-Value 0.0432
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value -0.5979
Confidence Interval (2-Sided) 95%
-1.1775 to -0.0184
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Cumulative Severe Hypoglycaemic Events Occurring From Randomisation by Visit
Hide Description A severe hypoglycaemic event was defined as an event with one of the following symptoms: "memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Time Frame Follow-ups at Weeks 13±1, 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 50 26
Mean (Standard Deviation)
Unit of Measure: events
FU week 13 Number Analyzed 49 participants 26 participants
0.0  (0.0) 0.0  (0.0)
FU Week 26 Number Analyzed 48 participants 25 participants
0.0  (0.14) 0.0  (0.20)
FU Week 52 Number Analyzed 49 participants 25 participants
0.1  (0.32) 0.0  (0.20)
9.Secondary Outcome
Title Proportion of Patients Maintaining a Residual β-cell Function
Hide Description

Maintenance of a residual ß-cell function is defined as at least one MMTT C-peptide value > 0.2 nmol/L.

Proportion is reported as Percentage of patients.

Time Frame Follow-ups at Weeks 13±1, 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo)
Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 49 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
FU Week 13 Number Analyzed 49 participants 26 participants
96.0
(86.29 to 99.51)
88.5
(69.85 to 97.55)
FU week 26 Number Analyzed 46 participants 25 participants
86.0
(73.26 to 94.18)
84.6
(65.13 to 95.64)
FU Week 52 Number Analyzed 45 participants 25 participants
78.0
(64.04 to 88.47)
76.9
(56.35 to 91.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 13
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1171
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 26
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6586
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5056
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
10.Secondary Outcome
Title Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit
Hide Description

A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

Proportion is reported as percentage of patients. Events per patient are calculated from the date of randomisation.

Time Frame Follow-ups at Weeks 13±1, 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo)
Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 49 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
FU Week 13 Number Analyzed 49 participants 25 participants
90.0
(78.19 to 96.67)
73.1
(52.21 to 88.43)
FU week 26 Number Analyzed 48 participants 24 participants
78.0
(64.04 to 88.47)
50.0
(29.93 to 70.07)
FU Week 52 Number Analyzed 47 participants 25 participants
62.0
(47.17 to 75.35)
53.8
(33.37 to 73.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments at week 13
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0779
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 26
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0248
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4504
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
11.Secondary Outcome
Title C-peptide AUC(15 to 120 Mins) Above Fasting Value
Hide Description

The means are all "adjusted means". The MMTT over the study: logAUC(15-120 min) of C-peptide above fasting value at Weeks 13±1, 26±2, and 52±2 is reported.

Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at weeks 13+/-1, 26±2 and 52±2

Time Frame Follow-ups at Weeks 13±1 26±2 and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 50 26
Mean (95% Confidence Interval)
Unit of Measure: log(ng*hr/ml [15-120 min]+1)
FU Week 13
3.3736
(3.1730 to 3.5742)
3.2334
(2.9568 to 3.5100)
FU week 26
3.2419
(3.0186 to 3.4652)
3.0649
(2.7562 to 3.3735)
FU week 52
2.9733
(2.7150 to 3.2316)
2.9282
(2.5720 to 3.2844)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 13
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with log(AUC(15-120 minutes)+1) of C-peptide above fasting value as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.4163
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 0.1402
Confidence Interval (2-Sided) 95%
-0.2015 to 0.4819
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 26
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with log(AUC(15-120 minutes)+1) of C-peptide above fasting value as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.3575
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 0.177
Confidence Interval (2-Sided) 95%
-0.2039 to 0.558
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 52
Type of Statistical Test Superiority
Comments Analysis is based on a linear mixed model for repeated measures with log(AUC(15-120 minutes)+1) of C-peptide above fasting value as dependent variable, treatment, visit and treatment by visit interaction as fixed effects and patient as random effect.
Statistical Test of Hypothesis P-Value 0.8386
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted mean difference
Estimated Value 0.0451
Confidence Interval (2-Sided) 95%
-0.3948 to 0.4851
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Area Under the Curve (AUC) (0-2 h) of C-peptide MMTT in Patients With Screening C-peptide < Median Value
Hide Description

A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening <median value. All the AUC analyses were based on actual rather than scheduled timings and were calculated using the trapezoidal rule. If the actual time was not recorded, the scheduled time was used instead. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal.

The 2-hour C-peptide AUC after the MMTT was transformed as log(x+1) values.

Time Frame Follow-up at Weeks 13±1, 26±2, and 52±2.
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 26 11
Mean (Standard Deviation)
Unit of Measure: log(ng*hr/ml [0-2 h]+1)
FU Week 13 Number Analyzed 26 participants 11 participants
3.8085  (0.45692) 3.4543  (0.86632)
FU Week 26 Number Analyzed 25 participants 10 participants
3.8202  (0.48142) 3.3178  (0.91906)
FU Week 52 Number Analyzed 24 participants 10 participants
3.3796  (0.68616) 3.1562  (0.97130)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 13
Type of Statistical Test Superiority
Comments Transformed AUC was analyzed with Student t-test for unpaired data using PROC TTEST within SAS® to compare Ladarixin and placebo groups. The estimated treatment difference between Ladarixin and placebo was also presented together with the corresponding 95% confidence interval.
Statistical Test of Hypothesis P-Value = 0.1114
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.354
Confidence Interval (2-Sided) 95%
-0.09 to 0.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 26
Type of Statistical Test Superiority
Comments Transformed AUC was analyzed with Student t-test for unpaired data using PROC TTEST within SAS® to compare Ladarixin and placebo groups. The estimated treatment difference between Ladarixin and placebo was also presented together with the corresponding 95% confidence interval.
Statistical Test of Hypothesis P-Value = 0.0411
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.502
Confidence Interval (2-Sided) 95%
0.02 to 0.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments At week 52
Type of Statistical Test Superiority
Comments Transformed AUC was analyzed with Student t-test for unpaired data using PROC TTEST within SAS® to compare Ladarixin and placebo groups. The estimated treatment difference between Ladarixin and placebo was also presented together with the corresponding 95% confidence interval.
Statistical Test of Hypothesis P-Value = 0.4506
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.223
Confidence Interval (2-Sided) 95%
-0.37 to 0.82
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Area Under the Curve (AUC) (15-120 Min) of C-peptide MMTT Above Fasting Value in Patients With Screening C-peptide < Median Value
Hide Description

A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening <median value. All the AUC analyses were based on actual rather than scheduled timings and were calculated using the trapezoidal rule. If the actual time was not recorded, the scheduled time was used instead.

Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at Weeks 13±1, 26±2, and 52±2.

Time Frame Follow-up at Weeks 13±1, 26±2, and 52±2.
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 26 11
Mean (Standard Deviation)
Unit of Measure: log(ng*hr/ml [15-120 min] +1)
FU week 13 Number Analyzed 26 participants 11 participants
3.1590  (0.56135) 2.7959  (1.07745)
FU week 26 Number Analyzed 25 participants 10 participants
27.7841  (15.10337) 18.6842  (15.46837)
FU week 52 Number Analyzed 24 participants 10 participants
2.7993  (0.82214) 19.9415  (16.95597)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Week 13 Analysis is based on a linear mixed model for repeated measures with log(AUC(15-120 minutes)+1) of C-peptide above fasting value as dependent variable, treatment, visit and treatment by visit interaction
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1847
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 0.3631
Confidence Interval (2-Sided) 95%
-0.1817 to 0.908
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Week 26 Analysis is based on a linear mixed model for repeated measures with log(AUC(15-120 minutes)+1) of C-peptide above fasting value as dependent variable, treatment, visit and treatment by visit interaction
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 0.6304
Confidence Interval (2-Sided) 95%
0.0609 to 1.1998
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Week 52 Analysis is based on a linear mixed model for repeated measures with log(AUC(15-120 minutes)+1) of C-peptide above fasting value as dependent variable, treatment, visit and treatment by visit interaction
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6299
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 0.1639
Confidence Interval (2-Sided) 95%
-0.5202 to 0.8479
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit in Patients With Screening C-peptide < Median Value
Hide Description

A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

Proportion is reported as percentage of patients, despite the measure type indicated is "number".

Events per patient are calculated from the date of randomisation.

Time Frame Follow-up at Weeks 13±1, 26±2, and 52±2
Hide Outcome Measure Data
Hide Analysis Population Description

ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo).

Please note that the number of participants analysed represents the number of patients contributing to summary statistics.

Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description:

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

Overall Number of Participants Analyzed 26 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
FU week 13 Number Analyzed 26 participants 11 participants
88.5
(69.85 to 97.55)
63.6
(30.79 to 89.07)
FU week 26 Number Analyzed 25 participants 9 participants
88.5
(69.85 to 97.55)
36.4
(10.93 to 69.21)
FU week 52 Number Analyzed 25 participants 10 participants
65.4
(44.33 to 82.79)
45.5
(16.75 to 76.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Week 13
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.163
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Week 26
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ladarixin, Placebo
Comments Week 52
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4437
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ladarixin Placebo
Hide Arm/Group Description

Ladarixin oral capsule

Ladarixin: Ladarixin oral capsule

Placebo oral capsule

Placebo: Placebo oral capsule

All-Cause Mortality
Ladarixin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/50 (0.00%)      0/26 (0.00%)    
Hide Serious Adverse Events
Ladarixin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/50 (6.00%)      1/26 (3.85%)    
Gastrointestinal disorders     
Gastrointestinal disorder  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Injury, poisoning and procedural complications     
Clavicle fracture  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Laceration  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Psychiatric disorders     
mental disorder  1  1/50 (2.00%)  1 0/26 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Ladarixin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   37/50 (74.00%)      21/26 (80.77%)    
Blood and lymphatic system disorders     
Anaemia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Eosinophilia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Iron deficiency anaemia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Lymphadenopathy  1  1/50 (2.00%)  2 0/26 (0.00%)  0
Lymphocytosis  1  0/50 (0.00%)  0 1/26 (3.85%)  2
Neutropenia  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Polycythaemia  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Cardiac disorders     
Palpitations  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Ear and labyrinth disorders     
Ear discomfort  1  1/50 (2.00%)  2 0/26 (0.00%)  0
Ear pain  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Gastrointestinal disorders     
abdominal discomfort  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Abdominal pain  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Abdominal pain upper  1  3/50 (6.00%)  4 2/26 (7.69%)  2
Constipation  1  2/50 (4.00%)  3 0/26 (0.00%)  0
Dental caries  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Diarrhoea  1  2/50 (4.00%)  2 2/26 (7.69%)  2
Dyspepsia  1  6/50 (12.00%)  9 0/26 (0.00%)  0
Dysphagia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Faeces hard  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Gatroesophageal reflux disease  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Hyperchlorhydria  1  2/50 (4.00%)  2 0/26 (0.00%)  0
Nausea  1  3/50 (6.00%)  4 3/26 (11.54%)  4
Odynophagia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Pancreatitis chronic  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Toothache  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Vomiting  1  2/50 (4.00%)  2 1/26 (3.85%)  1
General disorders     
Asthenia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Fatigue  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Injection site reaction  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Malaise  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Pyrexia  1  6/50 (12.00%)  7 2/26 (7.69%)  3
Sensation of foreign body  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Hepatobiliary disorders     
Hyperbilirubinaemia  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Immune system disorders     
Anaphylactic reaction  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Drug hypersensitivity  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Hypersensitivity  1  0/50 (0.00%)  0 2/26 (7.69%)  3
Infections and infestations     
Bronchitis  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Cystitis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Ear infection  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Eye infection  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Folliculitis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Gastroenteritis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Gastroeteritis viral  1  1/50 (2.00%)  1 3/26 (11.54%)  3
Gingivitis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Infected bite  1  1/50 (2.00%)  2 0/26 (0.00%)  0
Influenza  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Laryngitis  1  1/50 (2.00%)  1 1/26 (3.85%)  2
Oral herpes  1  2/50 (4.00%)  2 0/26 (0.00%)  0
Pharyngitis  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Sinusitis  1  0/50 (0.00%)  0 1/26 (3.85%)  2
Tinea pedis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Tonsillitis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Tooth abscess  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Upper respiratory tract infection  1  3/50 (6.00%)  3 1/26 (3.85%)  1
Urinary tract infection  1  2/50 (4.00%)  2 1/26 (3.85%)  1
Viral infection  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Viral upper respiratory tract infection  1  13/50 (26.00%)  19 4/26 (15.38%)  6
Injury, poisoning and procedural complications     
Alcohol poisoning  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Contusion  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Fall  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Joint injury  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Ligament sprain  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Limb injury  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Muscle injury  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Skin wound  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Sunburn  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Investigations     
Alanine aminotransferase increased  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Aspartate aminotransferase increased  1  2/50 (4.00%)  2 0/26 (0.00%)  0
Blood bilirubin increased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Blood iron decreased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
C-reactive protein increased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Eosinophil count decreased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Glycosylated haemoglobin increased  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Haemoglobin increased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Vitamin D decreased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Weight increased  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Metabolism and nutrition disorders     
Hypercholesterolaemia  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Hyperglycaemia  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Hypoglycaemia  1  4/50 (8.00%)  7 1/26 (3.85%)  2
Iron deficiency  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/50 (6.00%)  4 0/26 (0.00%)  0
Back pain  1  1/50 (2.00%)  1 1/26 (3.85%)  3
Muscle spasms  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Myalgia  1  1/50 (2.00%)  3 0/26 (0.00%)  0
Osteoarthritis  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Pain in extremity  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Nervous system disorders     
Dizziness  1  3/50 (6.00%)  3 1/26 (3.85%)  1
Headache  1  14/50 (28.00%)  20 6/26 (23.08%)  8
Migrane  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Syncope  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Psychiatric disorders     
Depression  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Emotional distress  1  2/50 (4.00%)  2 0/26 (0.00%)  0
Insomnia  1  2/50 (4.00%)  2 0/26 (0.00%)  0
Renal and urinary disorders     
Polyuria  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Reproductive system and breast disorders     
Breast pain  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Dysmenorrhoea  1  2/50 (4.00%)  4 0/26 (0.00%)  0
Nipple inflammation  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Cough  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Increased viscosity of upper respiratiory secretion  1  1/50 (2.00%)  4 0/26 (0.00%)  0
Oropharyngeal pain  1  4/50 (8.00%)  5 0/26 (0.00%)  0
Vocal cord inflammation  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Skin and subcutaneous tissue disorders     
Acne  1  1/50 (2.00%)  1 0/26 (0.00%)  0
Alopecia  1  1/50 (2.00%)  1 1/26 (3.85%)  1
Rash  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Surgical and medical procedures     
Diabetes mellitus management  1  0/50 (0.00%)  0 1/26 (3.85%)  1
Tooth extraction  1  2/50 (4.00%)  2 0/26 (0.00%)  0
Vascular disorders     
Hypertension  1  0/50 (0.00%)  0 1/26 (3.85%)  1
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pier Adelchi Ruffini, MD
Organization: Dompé Farmaceutici SpA
Phone: +39 02583831
EMail: pieradelchi.ruffini@dompe.com
Layout table for additonal information
Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT02814838    
Other Study ID Numbers: MEX0114
2014-003968-20 ( EudraCT Number )
First Submitted: June 13, 2016
First Posted: June 28, 2016
Results First Submitted: November 16, 2020
Results First Posted: January 12, 2021
Last Update Posted: January 12, 2021