REP0211: Study to Assess Efficacy & Safety of Reparixin in Pancreatic Islet Transplantation

• Sponsor: Dompé Farmaceutici S.p.A (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01817959
• Collaborator: (none)
• Enrollment: 51
• Locations: 9
• Arms: 2
• Duration (Months): 62
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The objective of this clinical trial was:

• to assess whether Reparixin leads to improved transplant outcome as measured by glycaemic control following intra-hepatic infusion of pancreatic islets in patients with Type 1 diabetes (T1D). The safety of Reparixin in the specific clinical setting was also evaluated.

Background: The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after organ transplantation. Reparixin is the first low molecular weight blocker of CXCL8 biological activity in clinical development. Thus, the use of reparixin may emerge as a potential key component in the sequentially integrated approach to immunomodulation and control of non specific inflammatory events surrounding the early phases of pancreatic islet transplantation in T1D patients.

Condition or Disease	Intervention/Treatment	Phase
Islet Transplantation in Diabetes Mellitus Type 1	Drug: Reparixin; Drug: Placebo	Phase 3

Detailed Description

Pancreatic islet transplantation has become a feasible option in the treatment of T1D which offers advantages over whole pancreas transplantation.

Several strategies are being evaluated, including anti-TNFα, aimed to prevent early inflammatory events that limit islet engraftment. Among possible mechanisms CXCL8 could play a crucial role in triggering the inflammatory reaction and might represent a relevant therapeutic target to prevent early graft failure.

Preliminary data obtained in transplanted patients recruited in the ongoing pilot trial coupled with the safety shown in human phase 1 and 2 studies provide a sound rationale for further development of reparixin in islet transplantation and prompted the conduct of this phase 3 clinical, multicentre, randomised, double-blind, parallel assignment study aimed at assessing the efficacy and safety of reparixin in preventing graft dysfunction after islet transplantation in T1D subjects.

At least 42 patients receiving pancreatic islet transplant were involved. Patients might receive up to 2 islet transplants, with the second transplant on average 6 months after the first one. Patients were randomly (2:1) assigned to receive either reparixin or placebo (control group). The Investigational Product was administered as an added on treatment to the immunosuppressant regimen.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Transplantation
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reparixin group Continuous iv infusion	Drug: Reparixin; Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.; Other Names: REP
Placebo Comparator: Placebo group Continuous iv infusion	Drug: Placebo; Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve (AUC) for the Serum C-peptide Level During the First 2 Hours of an MMTT (Mixed Meal Tolerance Test), Normalized by the Number of Islet Equivalent (IEQ)/kg [Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion]

   The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.

2. Area Under the Curve (AUC) for the Serum C-peptide Level During the First 2 Hours of an MMTT (Mixed Meal Tolerance Test), Normalized by the Number of Islet Equivalent (IEQ)/kg [Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 365±14 after the last islet infusion]

   The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.

Secondary Outcome Measures

1. Percentage of Insulin-independent Patients at Day 75 [Day 75±5 after the 1st and 2nd islet infusion]

   For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by: a glycated hemoglobin (HbA1c) level of less than 7%; a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period); a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).

2. Percentage of Insulin-independent Patients at Day 365 [Day 365±14 after last islet infusion]

   For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by: a glycated hemoglobin (HbA1c) level of less than 7%; a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period); a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).

3. Percentage of Patients Who Achieve and Maintain an HbA1c <7.0% (or a Reduction in HbA1c > 2%) AND Are Free of Severe Hypoglycaemic Events After Transplant in the Efficacy Population 1 [HbA1c at Day 365±14 after the last islet infusion; severe hypoglycaemic events from Day 75 to Day 365 after the last islet infusion]

   For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

4. Percentage of Patients Who Did Not Receive a 2nd Islet Infusion [Day 365±14 after the 1st islet infusion]

   This endpoint describes subjects who were not allocated to a 2nd islet infusion because they were insulin independent after the 1st islet infusion.

5. Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1 [Day 365±14 after the last islet infusion]

   The cumulative number of severe hypoglycaemic events after last transplant was assessed. For the purpose of this study, a severe hypoglycaemic event is 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 subject was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

6. Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

   Change from baseline is assessed as absolute decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.

7. Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

   Change from baseline is assessed as percentage decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.

8. Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

   Change from baseline in Glycated haemoglobin (HbA1c) was assessed as absolute decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.

9. Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion]

   Change from baseline in Glycated haemoglobin (HbA1c) was assessed as percentage decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.

10. Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

    Glucose levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.

11. Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

    C-peptide levels not normalized by the number of islet equivalent (IEQ)/kg were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.

12. Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

    Insulin levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.

13. β-cell Function as Assessed by β-score in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

    The β-score ranges from 0 (no graft function) to 8 (interpreted as an index of excellent graft function), and gives 0-2 points each for glucose, HbA1C, stimulated C-peptide and insulin requirement. Both for the total and partial scores the higher the score, the better the outcome. Fasting plasma glucose (mg/dL): ≤99 (Score 2); 100 - 124 (Score 1); ≥125 (Score 0); HbA1c (%): ≤6.1(Score 2); 6.2 - 6.9 (Score 1); ≥ 7.0 (Score 0); Daily average (previous week) insulin (IU/kg/day): --- (Score 2); 0.01 - 0.24 (score 1); ≥ 0.25 (Score 0) Stimulated C-peptide (ng/mL): ≥ 0.9; 0.3 - 0.89; ≤0.3

14. β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1 [Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion]

    TEF selects the two pivotal components of the β-score (DIR and A1C) and links them together through a simple description of how insulin supply influences the patient's glycemic control. TEF was evaluated by the following equation: TEF = a.DIR + b.HbA1c + c where DIR = daily insulin requirement (average in the previous week); a = -1; b = 1/-5.43; c = -a.DIR (pre-transplant) - b.HbA1c (pre-transplant)

Other Outcome Measures

1. Frequency of Patients Positive/Negative for Autoantibodies Against Glutamic Acid Decarboxylase (GAD) in Efficacy Population 1 [At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion]

   Auto-antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by immunoprecipitation of recombinant antigens. The Luminescent Immuno-Precipitation System based on chimeric autoantigens fused to luciferase enzyme was suggested as the preferred method to be used. Luciferase activity was measured in recovered immune-complex.

2. Frequency of Patients Positive/Negative for Autoantibodies Against Islet Antigen-2 (IA-2) in Efficacy Population 1 [At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion,]

   Auto-antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by immunoprecipitation of recombinant antigens. The Luminescent Immuno-Precipitation System based on chimeric autoantigens fused to luciferase enzyme was suggested as the preferred method to be used. Luciferase activity was measured in recovered immune-complex.

3. Frequency of Patients Positive/Negative for Autoantibodies Against Class I Human Leucocyte Antigen (HLA) in Efficacy Population 1 [Pre-transplant, day 75±5 after the 1st and 2nd islet infusion and day 365±14 after the last islet infusion]

   Anti-HLA antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by the Luminex analyzer. Class I and II positive/negative results were recorded.

4. Frequency of Patients Positive/Negative for Autoantibodies Against Class II Human Leucocyte Antigen (HLA) in Efficacy Population 1 [At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion,]

   Anti-HLA antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by the Luminex analyzer. Class I and II positive/negative results were recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ages 18-70 years, inclusive.

• Patients eligible for a pancreatic islet transplantation program

• Planned intrahepatic islet transplantation alone from a non-living donor with brain death.

• Patients willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.

• Patients who have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

Exclusion Criteria:

• Recipients of any previous transplant, including recipients of previous pancreatic islet transplantation.

• Recipients of islet from a non-heart beating donor.

• Pre-transplant average daily insulin requirement >1 IU/kg/day.

• Pre-transplant (the more recent value obtained within the 4 months prior to enrolment) HbA1c >11%.

• Patients with inadequate renal reserve as per calculated creatinine clearance (CLcr) < 60 mL/min according to the Cockcroft-Gault formula (1976).

• Patients with hepatic dysfunction as defined by increased ALT (alanine aminotranferase) / AST (aspartate aminotransferase) > 3 x upper limit of normal (ULN) and increased total bilirubin > 3mg/dL [>51.3 µmol/L]).

• Patients who receive treatment for a medical condition requiring chronic use of systemic steroids.

• Treatment with any anti-diabetic medication other than insulin within 4 weeks of transplant.

• Use of any investigational agent within 12 weeks of enrolment, including "anti-inflammatory" strategies (e.g. anti-TNFα, anti-IL-1 RA).

• Hypersensitivity to:

1. ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).

2. medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.

• Pregnant or breast-feeding women; unwillingness to use effective contraceptive measures (females and males).

Additional exclusion criteria specific for US centre.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago Medical Center, Department of Surgery, Division of Abdominal Organ Transplantation	Chicago	Illinois	United States	60637
2	Institute for Clinical and Experimental Medicine (IKEM), Diabetes Centre; Department of Diabetes.	Praha		Czechia	14021
3	Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele	Milan		Italy	20132
4	S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3	Milan		Italy	20162
5	Transplant Institute - Sahlgrenska University Hospital	Göteborg		Sweden	41345
6	Department of Nephrology and Transplantation; Skane University Hospital	Malmö		Sweden	20502
7	Department of Transplantation Surgery; The Karolinska University Hospital	Stockholm		Sweden	14186
8	Division for Transplantation and Liver Surgery; Department of Surgery; Uppsala University Hospital	Uppsala		Sweden	75185
9	Institute of Transplantation, Newcastle upon Tyne Hospitals - NHS Foundation Trust, Freeman Hospital	Newcastle upon Tyne		United Kingdom	NE7 7DN

Sponsors and Collaborators

• Dompé Farmaceutici S.p.A

Investigators

• Principal Investigator: Lorenzo PIEMONTI, MD, Dipartimento di Medicina Interna e Specialistica; IRCCS Ospedale San Raffaele
• Principal Investigator: Torbjörn LUNDGREN, MD, PhD, Department of Transplantation Surgery; The Karolinska University Hospital
• Principal Investigator: Gunnar TUFVESON, Professor, Department of Surgery; Uppsala University Hospital
• Principal Investigator: Ehab RAFAEL, MD, PhD, Department of Nephrology and Transplantation; Skane University Hospital
• Principal Investigator: James SHAW, Professor, Institute of Transplantation, Newcastle upon Tyne Hospitals - Freeman Hospital
• Principal Investigator: Frantisek SAUDEK, MD, DrSc, Institute for Clinical and Experimental Medicine (IKEM), Department of Diabetes.
• Principal Investigator: Piotr WITKOWSKI, MD, PhD, The University of Chicago Medical Center, Department of Surgery
• Principal Investigator: Federico BERTUZZI, MD, S.S.D. Diabetologia, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milano
• Principal Investigator: Bengt GUSTAFSSON, MD, PhD, Transplant Institute - Sahlgrenska University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dompé Farmaceutici S.p.A
• ClinicalTrials.gov Identifier: NCT01817959
• Other Study ID Numbers: REP0211; 2011-006201-10
• First Posted: Mar 26, 2013
• Last Update Posted: Sep 27, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Dompé Farmaceutici S.p.A: Pancreatic islet transplantation; Diabetes Mellitus Type 1; Islet transplantation graft survival & function
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1

Study Results

Participant Flow

Pre-assignment Detail	A total of 51 subjects were randomised into the trial. Three of these subjects did not have a transplant and never received randomised medication. Hence, a total of 48 subjects took trial medication and were included in the Safety Population.

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Period Title: Overall Study
STARTED	29	19
COMPLETED	25	16
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Reparixin Group	Placebo Group	Total
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.	Total of all reporting groups
Overall Participants	29	19	48
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 96.6%	18 94.7%	46 95.8%
>=65 years	1 3.4%	1 5.3%	2 4.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (11.3)	42.6 (10.8)	45.5 (11.2)
Sex: Female, Male (Count of Participants)
Female	17 58.6%	12 63.2%	29 60.4%
Male	12 41.4%	7 36.8%	19 39.6%
Region of Enrollment (participants) [Number]
Sweden	7 24.1%	6 31.6%	13 27.1%
Czechia	5 17.2%	3 15.8%	8 16.7%
United States	8 27.6%	4 21.1%	12 25%
Italy	7 24.1%	5 26.3%	12 25%
United Kingdom	2 6.9%	1 5.3%	3 6.3%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve (AUC) for the Serum C-peptide Level During the First 2 Hours of an MMTT (Mixed Meal Tolerance Test), Normalized by the Number of Islet Equivalent (IEQ)/kg
Description	The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.
Time Frame	Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 75±5 after the 1st islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Mean (Standard Deviation) [ng/mL/min]	0.247 (0.218)	0.321 (0.208)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9863
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.001
	Confidence Interval	(2-Sided) 99.75%; -0.205 to 0.207
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Curve (AUC) for the Serum C-peptide Level During the First 2 Hours of an MMTT (Mixed Meal Tolerance Test), Normalized by the Number of Islet Equivalent (IEQ)/kg
Description	The MMTT was to be performed ideally after an overnight fast. The test was to be initiated before 10 a.m. The Boost Original complete nutritional drink (Nestlé Nutrition) was used for the MMTT. Subjects were given 6 mL/kg of Boost preparation up to a maximum of 360 mL, to be drunk within 5 min. Blood samples for the C-peptide assay (the primary assessment) were withdrawn in fasting condition (basal), just prior to the meal (time 0, within 15 min prior to the meal) and then at 15, 30, 60, 90, 120 min after the meal.
Time Frame	Basal, -15' prior to meal, 15', 30', 60', 90', 120' following meal, Day 365±14 after the last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	24	15
Mean (Standard Deviation) [ng/mL/min]	0.234 (0.243)	0.207 (0.127)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7115
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.024
	Confidence Interval	(2-Sided) 99.75%; -0.184 to 0.232
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Insulin-independent Patients at Day 75
Description	For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by: a glycated hemoglobin (HbA1c) level of less than 7%; a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period); a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).
Time Frame	Day 75±5 after the 1st and 2nd islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
transplant 1	18.5 63.8%	5.6 29.5%
transplant 2	27.8 95.9%	53.3 280.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	Analytical statistics are reported for Day 75 after transplant 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1346
	Comments	Treatment p value
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.03 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Insulin-independent Patients at Day 365
Description	For the purpose of this study, insulin-independence is defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycaemic control, as defined by: a glycated hemoglobin (HbA1c) level of less than 7%; a glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than three times a week (based on measuring capillary glucose level a minimum of 7 times in a 7 day period); a glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than four times a week (based on measuring capillary glucose level 14 times in a 7 day period).
Time Frame	Day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	25	16
Number [percentage of participants]	32.0 110.3%	31.3 164.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9130
	Comments	Treatment p value
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.17 to 4.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Patients Who Achieve and Maintain an HbA1c <7.0% (or a Reduction in HbA1c > 2%) AND Are Free of Severe Hypoglycaemic Events After Transplant in the Efficacy Population 1
Description	For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Time Frame	HbA1c at Day 365±14 after the last islet infusion; severe hypoglycaemic events from Day 75 to Day 365 after the last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Number [Percentage of participants]	40.0 137.9%	50.0 263.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5467
	Comments	Treatment p value
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.16 to 2.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Patients Who Did Not Receive a 2nd Islet Infusion
Description	This endpoint describes subjects who were not allocated to a 2nd islet infusion because they were insulin independent after the 1st islet infusion.
Time Frame	Day 365±14 after the 1st islet infusion

Outcome Measure Data

Analysis Population Description

Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Number [percentage of participants]	14.8 51%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1383
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Cumulative Number of Severe Hypoglycaemic Events in the Efficacy Population 1
Description	The cumulative number of severe hypoglycaemic events after last transplant was assessed. For the purpose of this study, a severe hypoglycaemic event is 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 subject was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.
Time Frame	Day 365±14 after the last islet infusion

Outcome Measure Data

Analysis Population Description

Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	25	16
Mean (Standard Deviation) [number of events]	2.88 (8.23)	3.50 (7.65)

8. Secondary Outcome

Title	Absolute Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Description	Change from baseline is assessed as absolute decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
transplant 1	-0.231 (0.204)	-0.220 (0.203)
transplant 2	-0.389 (0.163)	-0.463 (0.168)
last transplant	-0.302 (0.167)	-0.375 (0.208)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is is the analytic statistics for Day 75 (Transplant 1)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6952
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.021
	Confidence Interval	(2-Sided) 95%; -0.130 to 0.088
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is is the analytic statistics for Day 75 (Transplant 2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5560
	Comments	This is a treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.028
	Confidence Interval	(2-Sided) 95%; -0.068 to 0.124
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 365 (last Transplant)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2537
	Comments	Treatment p value
	Method	ANCOVA
	Comments	Treatment p value
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.056
	Confidence Interval	(2-Sided) 95%; -0.042 to 0.154
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percent Change From Baseline in Average Daily Insulin Requirements in Efficacy Population 1
Description	Change from baseline is assessed as percentage decrease from pre-transplant levels. For the purpose of this study, daily insulin is averaged over the previous week.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Transplant 1	-42.5 (54.1)	-35.0 (35.3)
Transplant 2	-74.0 (28.6)	-27.7 (26.3)
Last transplant	-59.4 (35.8)	-63.7 (33.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 75 (Transplant 1)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5910
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-7.4
	Confidence Interval	(2-Sided) 95%; -35.2 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 75 (Transplant 2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5966
	Comments	Treatment p value
	Method	ANCOVA
	Comments	Treatment p value
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95%; -11.8 to 20.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 365 (last Transplant)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5005
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 95%; -12.1 to 24.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Absolute Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Description	Change from baseline in Glycated haemoglobin (HbA1c) was assessed as absolute decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Transplant 1	-1.58 (0.87)	-2.18 (1.23)
Transplant 2	-2.04 (1.10)	-2.81 (1.37)
Last Transplant	-1.30 (1.14)	-1.87 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 75 (Transplant 1)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3253
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 75 (Transplant 2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6069
	Comments	Treatment p value
	Method	least square mean difference
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; -0.46 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statics for Day 365 (last Transplant)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6437
	Comments	Treatment p value
	Method	ANCOVA
	Comments	Treatment p value
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Change in HbA1c % From Pre-transplant Levels in Efficacy Population 1
Description	Change from baseline in Glycated haemoglobin (HbA1c) was assessed as percentage decrease from pre-transplant levels. Diagnostic standards for HbA1c from American Diabetes Association are: <5.7% Normal; 5.7-6.4% prediabetes; >6.5 diabetes.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365+14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Transplant 1	-18.9 (9.5)	-24.0 (10.6)
Transplant 2	-24.4 (11.6)	-30.5 (11.7)
Last Transplant	-15.7 (13.1)	-20.9 (12.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 75 (Transplant 1)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4290
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -3.0 to 6.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 75 (Transplant 2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7853
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -6.3 to 8.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 365 (last Transplant)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6583
	Comments	Treatment p value
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -6.6 to 10.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Basal (Fasting) and 0 to 120 Min Time Course of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) in Efficacy Population 1
Description	Glucose levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Basal - day 75 - Transplant 1	120.6 (51.7)	118.9 (40.2)
15 min - day 75 - Transplant 1	146.0 (56.0)	132.5 (27.6)
30 min - day 75 - Transplant 1	191.6 (66.6)	168.1 (50.0)
60 min - day 75 - Transplant 1	236.9 (86.0)	219.1 (65.9)
90 min - day 75 - Transplant 1	254.0 (110.1)	245.0 (84.7)
120 min - day 75 - Transplant 1	264.1 (116.7)	246.0 (84.4)
Basal - day 75 - Transplant 2	103.8 (19.8)	112.8 (18.6)
15 min - day 75 - Transplant 2	130.0 (22.3)	134.8 (26.8)
30 min - day 75 - Transplant 2	166.7 (33.6)	157.8 (32.6)
60 min - day 75 - Transplant 2	189.1 (57.9)	172.0 (70.9)
90 min - day 75 - Transplant 2	191.8 (72.8)	175.1 (99.7)
120 min - day 75 - Transplant 2	188.0 (88.1)	171.7 (104.8)
Basal - day 365 - Last transplant	112.2 (37.6)	125.1 (64.5)
15 min - day 365 - Last transplant	139.5 (43.1)	146.7 (68.9)
30 min - day 365 - Last transplant	180.1 (53.9)	182.7 (80.2)
60 min - day 365 - Last transplant	221.2 (81.2)	213.6 (106.2)
90 min - day 365 - Last transplant	235.7 (112.6)	222.0 (122.6)
120 min - day 365 - Transplant 2	239.9 (127.6)	205.5 (104.3)

13. Secondary Outcome

Title	Basal (Fasting) and 0 to 120 Min Time Course of C-peptide (Non-normalized) Derived From the MMTT in Efficacy Population 1
Description	C-peptide levels not normalized by the number of islet equivalent (IEQ)/kg were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Basal - day 75 - Transplant 1	0.50 (0.46)	0.51 (0.44)
15 min - day 75 - Transplant 1	0.71 (0.77)	0.67 (0.71)
30 min - day 75 - Transplant 1	1.18 (1.32)	0.89 (0.90)
60 min - day 75 - Transplant 1	1.66 (1.80)	1.46 (1.43)
90 min - day 75 - Transplant 1	1.81 (1.64)	1.80 (1.57)
120 min - day 75 - Transplant 1	1.72 (1.34)	2.04 (1.64)
Basal - day 75 - Transplant 2	0.93 (0.69)	1.27 (0.50)
15 min - day 75 - Transplant 2	1.42 (1.36)	1.73 (0.78)
30 min - day 75 - Transplant 2	2.13 (1.90)	2.55 (1.19)
60 min - day 75 - Transplant 2	2.98 (2.15)	3.65 (2.09)
90 min - day 75 - Transplant 2	3.30 (2.15)	3.56 (1.96)
120 min - day 75 - Transplant 2	3.33 (1.98)	2.90 (1.28)
Basal - day 365 - Last transplant	0.76 (0.65)	1.14 (0.62)
15 min - day 365 - Last transplant	1.06 (1.02)	1.32 (0.90)
30 min - day 365 - Last transplant	1.65 (1.66)	2.17 (1.50)
60 min - day 365 - Last transplant	2.37 (2.38)	2.88 (181)
90 min - day 365 - Last transplant	2.47 (2.27)	3.13 (1.84)
120 min - day 365 - Transplant 2	2.11 (1.74)	3.12 (1.68)

14. Secondary Outcome

Title	Basal (Fasting) and 0 to 120 Min Time Course of Insulin Derived From the MMTT in Efficacy Population 1
Description	Insulin levels were measured at the baseline in fasting condition, and at the following timepoints: 15, 30, 60, 90, 120 min after mixed meal at the hereunder reported time frame.
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
Basal - day 75 - Transplant 1	16.5 (43.6)	15.2 (39.8)
15 min - day 75 - Transplant 1	13.5 (16.6)	11.8 (13.2)
30 min - day 75 - Transplant 1	21.0 (27.7)	15.8 (16.9)
60 min - day 75 - Transplant 1	25.6 (32.9)	23.0 (24.4)
90 min - day 75 - Transplant 1	23.9 (27.4)	22.3 (18.8)
120 min - day 75 - Transplant 1	21.3 (28.2)	23.1 (18.1)
Basal - day 75 - Transplant 2	8.4 (10.3)	9.0 (3.8)
15 min - day 75 - Transplant 2	16.0 (16.0)	17.5 (12.1)
30 min - day 75 - Transplant 2	28.4 (30.0)	31.1 (17.8)
60 min - day 75 - Transplant 2	33.7 (23.4)	37.8 (20.4)
90 min - day 75 - Transplant 2	36.3 (23.6)	31.2 (20.6)
120 min - day 75 - Transplant 2	29.7 (19.2)	25.3 (10.4)
Basal - day 365 - Last transplant	7.5 (7.6)	6.2 (4.0)
15 min - day 365 - Last transplant	13.8 (17.0)	10.8 (9.0)
30 min - day 365 - Last transplant	19.4 (19.2)	20.7 (13.1)
60 min - day 365 - Last transplant	28.5 (30.1)	25.6 (14.3)
90 min - day 365 - Last transplant	25.8 (23.5)	26.1 (17.8)
120 min - day 365 - Transplant 2	19.9 (18.4)	27.1 (11.8)

15. Secondary Outcome

Title	β-cell Function as Assessed by β-score in Efficacy Population 1
Description	The β-score ranges from 0 (no graft function) to 8 (interpreted as an index of excellent graft function), and gives 0-2 points each for glucose, HbA1C, stimulated C-peptide and insulin requirement. Both for the total and partial scores the higher the score, the better the outcome. Fasting plasma glucose (mg/dL): ≤99 (Score 2); 100 - 124 (Score 1); ≥125 (Score 0); HbA1c (%): ≤6.1(Score 2); 6.2 - 6.9 (Score 1); ≥ 7.0 (Score 0); Daily average (previous week) insulin (IU/kg/day): --- (Score 2); 0.01 - 0.24 (score 1); ≥ 0.25 (Score 0) Stimulated C-peptide (ng/mL): ≥ 0.9; 0.3 - 0.89; ≤0.3
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
day 75 - Transplant 1	4.19 (2.37)	4.06 (2.29)
day 75 - Transplant 2	5.53 (1.42)	5.67 (2.06)
day 365 - Last transplant	4.63 (2.50)	5.13 (2.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 75 (Transplant 1)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9949
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -1.28 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 75 (Transplant 2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8753
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -1.18 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 365 (last Transplant)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3955
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -1.97 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	β-cell Function as Assessed by Transplant Estimated Function (TEF) in Efficacy Population 1
Description	TEF selects the two pivotal components of the β-score (DIR and A1C) and links them together through a simple description of how insulin supply influences the patient's glycemic control. TEF was evaluated by the following equation: TEF = a.DIR + b.HbA1c + c where DIR = daily insulin requirement (average in the previous week); a = -1; b = 1/-5.43; c = -a.DIR (pre-transplant) - b.HbA1c (pre-transplant)
Time Frame	Day 75±5 after the 1st and 2nd islet infusion and day 365±14 after last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
day 75 - Transplant 1	0.523 (0.260)	0.621 (0.332)
day 75 - Transplant 2	0.764 (0.240)	0.981 (0.275)
day 365 - Last transplant	0.539 (0.320)	0.719 (0.359)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 75 (Transplant 1)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2444
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.105
	Confidence Interval	(2-Sided) 95%; -0.286 to 0.075
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 75 (Transplant 2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0328
	Comments	Treatment p value
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.218
	Confidence Interval	(2-Sided) 95%; -0.417 to -0.019
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Reparixin Group, Placebo Group
	Comments	This is the analytic statistics for Day 365 (last Transplant)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1059
	Comments	This is the analytic statistics for Day 75 (Transplant 2)
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.177
	Confidence Interval	(2-Sided) 95%; -0.393 to 0.039
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Other Pre-specified Outcome

Title	Frequency of Patients Positive/Negative for Autoantibodies Against Glutamic Acid Decarboxylase (GAD) in Efficacy Population 1
Description	Auto-antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by immunoprecipitation of recombinant antigens. The Luminescent Immuno-Precipitation System based on chimeric autoantigens fused to luciferase enzyme was suggested as the preferred method to be used. Luciferase activity was measured in recovered immune-complex.
Time Frame	At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
pre-transplant 1 - positive	48.1 165.9%	52.9 278.4%
pre-transplant 1 - negative	51.9 179%	47.1 247.9%
day 75 - Transplant 1 - positive	69.2 238.6%	64.7 340.5%
day 75 - Transplant 1 - negative	30.8 106.2%	35.3 185.8%
pre-transplant 2 - positive	66.7 230%	62.5 328.9%
pre-transplant 2 - negative	33.3 114.8%	37.5 197.4%
day 75 - Transplant 2 - positive	66.7 230%	53.3 280.5%
day 75 - Transplant 2 - negative	33.3 114.8%	46.7 245.8%
day 365 - Last transplant - positive	56.0 193.1%	50.0 263.2%
day 365 - Last transplant - negative	44.0 151.7%	50.0 263.2%

18. Other Pre-specified Outcome

Title	Frequency of Patients Positive/Negative for Autoantibodies Against Islet Antigen-2 (IA-2) in Efficacy Population 1
Description	Auto-antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by immunoprecipitation of recombinant antigens. The Luminescent Immuno-Precipitation System based on chimeric autoantigens fused to luciferase enzyme was suggested as the preferred method to be used. Luciferase activity was measured in recovered immune-complex.
Time Frame	At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion,

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
pre-transplant 1 - positive	22.2 76.6%	14.3 75.3%
pre-transplant 1 - negative	77.8 268.3%	85.7 451.1%
day 75 - Transplant 1 - positive	28.0 96.6%	20.0 105.3%
day 75 - Transplant 1 - negative	72.0 248.3%	80.0 421.1%
pre-transplant 2 - positive	22.2 76.6%	13.3 70%
pre-transplant 2 - negative	77.8 268.3%	86.7 456.3%
day 75 - Transplant 2 - positive	27.8 95.9%	14.3 75.3%
day 75 - Transplant 2 - negative	72.2 249%	85.7 451.1%
day 365 - Last transplant - positive	20.0 69%	20.0 105.3%
day 365 - Last transplant - negative	80.0 275.9%	80.0 421.1%

19. Other Pre-specified Outcome

Title	Frequency of Patients Positive/Negative for Autoantibodies Against Class I Human Leucocyte Antigen (HLA) in Efficacy Population 1
Description	Anti-HLA antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by the Luminex analyzer. Class I and II positive/negative results were recorded.
Time Frame	Pre-transplant, day 75±5 after the 1st and 2nd islet infusion and day 365±14 after the last islet infusion

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
pre-transplant 1 - positive	15.4 53.1%	27.8 146.3%
pre-transplant 1 - negative	84.6 291.7%	72.2 380%
day 75 - Transplant 1 - positive	20.0 69%	23.5 123.7%
day 75 - Transplant 1 - negative	80.0 275.9%	76.5 402.6%
pre-transplant 2 - positive	29.4 101.4%	31.3 164.7%
pre-transplant 2 - negative	70.6 243.4%	68.8 362.1%
day 75 - Transplant 2 - positive	33.3 114.8%	26.7 140.5%
day 75 - Transplant 2 - negative	66.7 230%	73.3 385.8%
day 365 - Last transplant - positive	28.0 96.6%	26.7 140.5%
day 365 - Last transplant - negative	72.0 248.3%	73.3 385.8%

20. Other Pre-specified Outcome

Title	Frequency of Patients Positive/Negative for Autoantibodies Against Class II Human Leucocyte Antigen (HLA) in Efficacy Population 1
Description	Anti-HLA antibodies were assayed on cell-free serum samples obtained as per centre practice ideally by the Luminex analyzer. Class I and II positive/negative results were recorded.
Time Frame	At pre-transplant, Day 75±5 after the 1st and 2nd islet infusion and Day 365±14 days after the last islet infusion,

Outcome Measure Data

Analysis Population Description

The Efficacy Population 1 consisted of all subjects who were randomised, received the IP (either Reparixin or placebo), and had a transplant (either one or two).

Arm/Group Title	Reparixin Group	Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.	Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
Measure Participants	27	18
pre-transplant 1 - positive	7.7 26.6%	5.6 29.5%
pre-transplant 1 - negative	92.3 318.3%	94.4 496.8%
day 75 - Transplant 1 - positive	16.0 55.2%	12.5 65.8%
day 75 - Transplant 1 - negative	84.0 289.7%	87.5 460.5%
pre-transplant 2 - positive	5.9 20.3%	6.3 33.2%
pre-transplant 2 - negative	94.1 324.5%	93.8 493.7%
day 75 - Transplant 2 - positive	16.7 57.6%	6.7 35.3%
day 75 - Transplant 2 - negative	83.3 287.2%	93.3 491.1%
day 365 - Last transplant - positive	20.0 69%	20.0 105.3%
day 365 - Last transplant - negative	80.0 275.9%	80.0 421.1%

Adverse Events

Arm/Group Title	Reparixin Group		Placebo Group
Arm/Group Description	Continuous iv infusion Reparixin: Continuous i.v. infusion into a central vein for 7 days, starting approximately 12 hrs (6-18 hrs) before each pancreatic islet infusion.The Investigational Product (IP) were to be administered as an add-on treatment for the immunosuppressant regimen.		Continuous iv infusion Placebo: Continuous infusion at a volume/rate matching active treatment.The placebo was to be administered as well as an add-on treatment for the immunosuppressant regimen.
All Cause Mortality
	Reparixin Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/19 (0%)
Serious Adverse Events
	Reparixin Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/29 (58.6%)		12/19 (63.2%)
Blood and lymphatic system disorders
Anaemia	3/29 (10.3%)	4	1/19 (5.3%)	2
Leukopenia	1/29 (3.4%)	1	1/19 (5.3%)	1
Neutropenia	1/29 (3.4%)	1	1/19 (5.3%)	1
Gastrointestinal disorders
Abdominal pain	2/29 (6.9%)	2	1/19 (5.3%)	1
Abdominal pain upper	1/29 (3.4%)	1	0/19 (0%)	0
Diarrhoea	2/29 (6.9%)	2	0/19 (0%)	0
Intra-abdominal haemmorrhage	2/29 (6.9%)	2	2/19 (10.5%)	2
Nausea	1/29 (3.4%)	1	1/19 (5.3%)	3
Vomiting	2/29 (6.9%)	2	1/19 (5.3%)	2
Peritoneal haemorrhage	2/29 (6.9%)	2	1/19 (5.3%)	1
General disorders
Implant site haemorrhage	1/29 (3.4%)	1	0/19 (0%)	0
Multiple organ dysfunction syndrome	1/29 (3.4%)	1	0/19 (0%)	0
Oedema peripheral	1/29 (3.4%)	1	0/19 (0%)	0
Puncture site haemorrhage	0/29 (0%)	0	1/19 (5.3%)	1
Pyrexia	0/29 (0%)	0	1/19 (5.3%)	1
Hepatobiliary disorders
Hepatic haematoma	0/29 (0%)	0	1/19 (5.3%)	1
Immune system disorders
Alloimmunisation	2/29 (6.9%)	2	0/19 (0%)	0
Drug Hypersensititity	0/29 (0%)	0	1/19 (5.3%)	1
Transplant rejection	1/29 (3.4%)	1	0/19 (0%)	0
Infections and infestations
Localised infection	0/29 (0%)	0	1/19 (5.3%)	1
Pneumonia	0/29 (0%)	0	1/19 (5.3%)	1
Sepsis	1/29 (3.4%)	1	1/19 (5.3%)	1
Streptococcal sepsis	0/29 (0%)	0	1/19 (5.3%)	1
Urinary Tract Infection	0/29 (0%)	0	1/19 (5.3%)	1
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/29 (3.4%)	1	0/19 (0%)	0
Complications of transplant surgery	1/29 (3.4%)	1	0/19 (0%)	0
Upper limb fracture	1/29 (3.4%)	1	0/19 (0%)	0
Investigations
HLA marker study positive	1/29 (3.4%)	1	0/19 (0%)	0
Hepatic enzyme increased	1/29 (3.4%)	1	0/19 (0%)	0
Panel-reactive antibody increased	0/29 (0%)	0	1/19 (5.3%)	1
Metabolism and nutrition disorders
Dehydration	0/29 (0%)	0	1/19 (5.3%)	3
Hypoglycemia	1/29 (3.4%)	1	0/19 (0%)	0
Ketosis	0/29 (0%)	0	1/19 (5.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/29 (3.4%)	1	0/19 (0%)	0
Nervous system disorders
Diabetic neuropathy	1/29 (3.4%)	1	0/19 (0%)	0
Generalised tonic-clonic seizure	1/29 (3.4%)	1	0/19 (0%)	0
Headache	2/29 (6.9%)	2	0/19 (0%)	0
Psychiatric disorders
Acute psychosis	1/29 (3.4%)	1	0/19 (0%)	0
Renal and urinary disorders
Urinary retantion	0/29 (0%)	0	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal ache	0/29 (0%)	0	1/19 (5.3%)	1
Pulmonary embolism	0/29 (0%)	0	1/19 (5.3%)	1
Vascular disorders
Haemorrhage	1/29 (3.4%)	1	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Reparixin Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		18/19 (94.7%)
Blood and lymphatic system disorders
Anaemia	6/29 (20.7%)	6	2/19 (10.5%)	4
Leukopenia	0/29 (0%)	0	1/19 (5.3%)	1
Neutropenia	1/29 (3.4%)	1	2/19 (10.5%)	2
Cardiac disorders
Angina pectoris	1/29 (3.4%)	1	0/19 (0%)	0
Bradycardia	1/29 (3.4%)	1	0/19 (0%)	0
Tachycardia	2/29 (6.9%)	3	1/19 (5.3%)	1
Eye disorders
Vision blurred	0/29 (0%)	0	1/19 (5.3%)	1
Vitreous floaters	0/29 (0%)	0	1/19 (5.3%)	1
Gastrointestinal disorders
Abdominal pain	7/29 (24.1%)	7	7/19 (36.8%)	9
Abdominal pain upper	1/29 (3.4%)	1	2/19 (10.5%)	2
Constipation	3/29 (10.3%)	3	0/19 (0%)	0
Diarrhoea	7/29 (24.1%)	8	2/19 (10.5%)	3
Lip oedema	1/29 (3.4%)	1	0/19 (0%)	0
Lip swelling	1/29 (3.4%)	1	0/19 (0%)	0
Nausea	13/29 (44.8%)	17	12/19 (63.2%)	15
Stomatitis	2/29 (6.9%)	2	1/19 (5.3%)	1
Vomiting	7/29 (24.1%)	7	6/19 (31.6%)	6
General disorders
Catheter site haemorrhage	1/29 (3.4%)	1	1/19 (5.3%)	1
Catheter site pain	3/29 (10.3%)	4	2/19 (10.5%)	2
Chest discomfort	1/29 (3.4%)	1	0/19 (0%)	0
Chills	1/29 (3.4%)	1	0/19 (0%)	0
Fatigue	1/29 (3.4%)	1	0/19 (0%)	0
Generalised oedema	1/29 (3.4%)	1	0/19 (0%)	0
Implant site haemorrhage	1/29 (3.4%)	1	0/19 (0%)	0
Malaise	4/29 (13.8%)	5	1/19 (5.3%)	1
Peripheral swelling	1/29 (3.4%)	1	0/19 (0%)	0
Pyrexia	3/29 (10.3%)	4	6/19 (31.6%)	6
Vessel puncture site erythema	1/29 (3.4%)	1	0/19 (0%)	0
Hepatobiliary disorders
Hepatic haemorrhage	1/29 (3.4%)	2	0/19 (0%)	0
Infections and infestations
Coccidioidomycosis	1/29 (3.4%)	1	0/19 (0%)	0
Urinary tract infection	1/29 (3.4%)	1	0/19 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/29 (0%)	0	1/19 (5.3%)	1
Fall	1/29 (3.4%)	1	0/19 (0%)	0
Head injury	1/29 (3.4%)	1	0/19 (0%)	0
Incision site pain	1/29 (3.4%)	1	0/19 (0%)	0
Post procedural heamatoma	0/29 (0%)	0	1/19 (5.3%)	1
Procedural pain	3/29 (10.3%)	3	1/19 (5.3%)	2
Wound Dehiscence	0/29 (0%)	0	1/19 (5.3%)	1
Investigations
Aspartate aminotransferase increased	1/29 (3.4%)	1	0/19 (0%)	0
Blood creatinine increased	3/29 (10.3%)	3	0/19 (0%)	0
Blood magnesium decreased	0/29 (0%)	0	1/19 (5.3%)	1
Blood potassium decreased	0/29 (0%)	0	1/19 (5.3%)	1
Blood pressure decreased	0/29 (0%)	0	1/19 (5.3%)	1
C-reactive protein increased	1/29 (3.4%)	1	1/19 (5.3%)	1
Heart rate increased	0/29 (0%)	0	1/19 (5.3%)	1
Hepatic enzyme increased	0/29 (0%)	0	2/19 (10.5%)	2
Liver function test increased	0/29 (0%)	0	1/19 (5.3%)	1
Portal vein presssure increased	2/29 (6.9%)	2	1/19 (5.3%)	1
Weight increased	0/29 (0%)	0	2/19 (10.5%)	2
Metabolism and nutrition disorders
Decreased appetite	1/29 (3.4%)	1	0/19 (0%)	0
Fluid retention	1/29 (3.4%)	1	0/19 (0%)	0
Hyperkalaemia	3/29 (10.3%)	5	0/19 (0%)	0
Hypervolaemia	0/29 (0%)	0	1/19 (5.3%)	1
Hypoglycaemia	6/29 (20.7%)	6	3/19 (15.8%)	5
Hypokalaemia	0/29 (0%)	0	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/29 (3.4%)	1	0/19 (0%)	0
Back pain	2/29 (6.9%)	3	2/19 (10.5%)	3
joint swelling	1/29 (3.4%)	1	0/19 (0%)	0
Muscular weakness	0/29 (0%)	0	1/19 (5.3%)	1
Musculoskeletal pain	3/29 (10.3%)	3	1/19 (5.3%)	1
Neck pain	1/29 (3.4%)	1	0/19 (0%)	0
Pain in extremity	1/29 (3.4%)	1	1/19 (5.3%)	1
Nervous system disorders
Dizziness	0/29 (0%)	0	1/19 (5.3%)	1
Dysgeusia	1/29 (3.4%)	1	0/19 (0%)	0
Headache	8/29 (27.6%)	11	7/19 (36.8%)	9
Migrane	1/29 (3.4%)	1	2/19 (10.5%)	2
Syncope	1/29 (3.4%)	1	0/19 (0%)	0
Tremor	1/29 (3.4%)	1	0/19 (0%)	0
Psychiatric disorders
Anxiety	1/29 (3.4%)	1	3/19 (15.8%)	4
Emotional distress	0/29 (0%)	0	1/19 (5.3%)	1
Insomnia	1/29 (3.4%)	2	2/19 (10.5%)	2
Renal and urinary disorders
Urinary retention	0/29 (0%)	0	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/29 (0%)	0	1/19 (5.3%)	1
Epistaxis	2/29 (6.9%)	2	1/19 (5.3%)	1
Nasal congestion	2/29 (6.9%)	2	0/19 (0%)	0
Rhinorrhoea	1/29 (3.4%)	1	0/19 (0%)	0
Upper-airway cough syndrome	1/29 (3.4%)	1	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Acne	1/29 (3.4%)	1	1/19 (5.3%)	1
Erythema	1/29 (3.4%)	1	0/19 (0%)	0
Hyperhidrosis	1/29 (3.4%)	1	0/19 (0%)	0
Pruritus	2/29 (6.9%)	2	2/19 (10.5%)	2
Rash	0/29 (0%)	0	1/19 (5.3%)	1
Skin esfoliation	0/29 (0%)	0	1/19 (5.3%)	1
Hypertension	3/29 (10.3%)	4	0/19 (0%)	0
Vascular disorders
Hot flush	1/29 (3.4%)	1	1/19 (5.3%)	1
Hypotension	2/29 (6.9%)	2	0/19 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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.