Phase 3
N=104
Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation
Pancreatectomy for Chronic Pancreatitis
Bottom Line
View on ClinicalTrials.gov: NCT01967888 ↗Enrolled (actual)
104
Serious AEs
57.8%
Results posted
Oct 2019
Primary outcome: Primary: Percentage of Patients Who Were Insulin Independent After Islet Autotransplantation (IAT) at Day 365±14 Days After Transplant. — 20.0; 21.2 Percentage of participants — p=0.542
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Reparixin (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Dompé Farmaceutici S.p.A
- Primary completion
- Jan 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Patients Who Were Insulin Independent After Islet Autotransplantation (IAT) at Day 365±14 Days After Transplant. |
20.0; 21.2 | 0.542 |
| SECONDARY Area Under the Curve (AUC) for the Serum C-peptide Level at Day 75±14 After the Transplant |
0.5314796; 0.6827533 | 0.092 |
| SECONDARY Area Under the Curve (AUC) for the Serum C-peptide Level at Day 365±14 After the Transplant |
0.5563432; 0.6865954 | 0.161 |
| SECONDARY Average Daily Insulin Requirements at Day 75±14 After the Transplant |
0.2125; 0.2190 | 0.846 |
| SECONDARY Average Daily Insulin Requirements at Day 365±14 After the Transplant |
0.1723; 0.1823 | 0.817 |
| SECONDARY Time Course From Basal to 240 Min of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) at Day 75±14 After the Transplant |
157.0894; 166.5535 | 0.570 |
| SECONDARY Time Course From Basal to 240 Min of Glucose Derived From the Mixed Meal Tolerance Test (MMTT) at Day 365±14 After the Transplant |
157.9988; 180.9442 | =0.074 |
| SECONDARY Time Course From Basal to 240 Min of C-peptide Derived From the Mixed Meal Tolerance Test (MMTT) at Day 75±14 After the Transplant |
1.8976; 2.1051 | =0.358 |
| SECONDARY Time Course From Basal to 240 Min of C-peptide Derived From the Mixed Meal Tolerance Test (MMTT) at Day 365±14 After the Transplant |
1.6052; 1.8822 | =0.288 |
| SECONDARY Time Course From Basal to 240 Min of Insulin Derived From the Mixed Meal Tolerance Test (MMTT) at Day 75±14 After the Transplant |
23.67209; 23.57493 | =0.980 |
| SECONDARY Time Course From Basal to 240 Min of Insulin Derived From the Mixed Meal Tolerance Test (MMTT) at Day 365±14 After the Transplant |
22.85522; 21.77905 | =0.785 |
| SECONDARY β-cell Function at Day 75±14 After the Transplant |
5.7; 5.2 | 0.176 |
| SECONDARY β-cell Function at Day 365±14 After the Transplant |
5.9; 5.4 | 0.403 |
| SECONDARY Proportion of Patients With an HbA1c <6.5% at Day 365±14 After the Transplant |
64.3; 62.2 | 0.842 |
| SECONDARY Cumulative Number of Severe Hypoglycemic Events From Day 75±14 to Day 365±14 After the Transplant |
0.1; 0.0 | 0.339 |
| SECONDARY Proportion of Patients With an HbA1c <6.5% at Day 365±14 After the Transplant AND Free of Severe Hypoglycemic Events From Day 75±14 to Day 365±14 After the Transplant Inclusive |
64.1; 59.1 | 0.640 |
| SECONDARY Incidence and Severity of Adverse Events and Serious Adverse Events Throughout the Study |
90.0; 92.3; 90.0; 80.8; 64.0; 53.8 | — |
| SECONDARY Proportion of Patients Falling Into One of the Following Malnutrition Risk Levels (Poor Prognosis, Significant Risk, Increased Risk, Normal) According to Pre-albumin Level at Day 75±14 After the Transplant |
0; 0; 9.5; 4.3; 45.2; 28.3 | — |
| SECONDARY Proportion of Patients Falling Into One of the Following Malnutrition Risk Levels (Poor Prognosis, Significant Risk, Increased Risk, Normal) According to Pre-albumin Level at Day 365±14 After the Transplant |
5.0; 0; 2.5; 6.8; 27.5; 9.1 | — |
| SECONDARY Proportion of Patients by Steatorrhea Severity at Day 75±14 After the Transplant |
54.5; 64.6; 29.5; 25.0; 11.4; 6.3 | — |
| SECONDARY Proportion of Patients by Steatorrhea Severity at Day 365±14 After the Transplant |
52.4; 58.7; 26.2; 19.6; 21.4; 21.7 | — |
| SECONDARY Cumulative Number of Episodes of Documented Asymptomatic Hypoglycemia From Day 75±14 to Day 365±14 After the Transplant |
1.5; 4.4 | 0.448 |
| SECONDARY Cumulative Number of Episodes of Documented Symptomatic Hypoglycemia From Day 75±14 to Day 365±14 After the Transplant |
4.6; 4.8 | 0.910 |
| SECONDARY Cumulative Number of Diabetic Ketoacidosis-related Events |
0.0; 0.0 | 1.000 |
| SECONDARY Peak C-peptide at Day 75 After the Transplant |
2.640; 2.900 | — |
| SECONDARY Peak C-peptide at Day 365 After the Transplant |
2.630; 3.170 | — |
| SECONDARY Time-to-peak C-peptide at Day 75 After the Transplant |
104.2; 108.7 | — |
| SECONDARY Time-to-peak C-peptide at Day 365 After the Transplant |
97.8; 102.0 | — |
| SECONDARY Change From Baseline in Post-transplant Alanine Aminotransferase (ALT) |
60.4105; 29.0615 | =0.5018 |
| SECONDARY Change From Baseline in Post-transplant Aspartate Aminotransferase (AST) |
46.8755; 23.3301 | =0.4537 |
| SECONDARY Number of Treatment Emergent Adverse Events Related to Investigational Product |
20; 28; 0; 0; 0; 0 | — |
| SECONDARY Number of Serious Treatment Emergent Adverse Events Related to Investigational Product |
4; 1; 0; 0; 0; 0 | — |
Summary
The study is a phase 2/3, multicenter, double-blind, parallel assignment study. It involves 100 adult recipients of an intra-hepatic pancreatic Islet Auto-Transplantation (IAT).
The objective of this clinical trial is to assess whether reparixin leads to improved transplant outcome as measured by the proportion of insulin-independent patients following IAT. The safety of reparixin in the specific clinical setting will be also evaluated.
Eligibility Criteria
Inclusion Criteria
- Patients eligible for an IAT following total (or completion) pancreatectomy.
- Ages > 18 years.
- 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 a previous IAT (if completion pancreatectomy).
- Patients undergoing total pancreatectomy due to either pancreatic cancer or pancreatic benign diseases other than chronic pancreatitis, including insulinomas, etc.
- Patients with inadequate renal reserve as per calculated creatinine clearance (CLcr) 3 x upper limit of normal (ULN) or increased total bilirubin above the upper limit at local laboratory). Patients with Gilbert's syndrome (elevated unconjugated bilirubin levels in the absence of any evidence of hepatic or biliary tract disease) are not excluded.
- Patients with a preoperative International Normalized Ratio (INR) > 1.5 or any known coagulopathy.
- Hypersensitivity to:
- ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).
- medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.
- Concurrent sepsis (as per positive blood culture(s) and/or fever associated with other signs of systemic sepsis syndrome).
- Treatment with systemic steroids in the 2 weeks prior to enrolment (except for the use of 115 mg/dL and/or a HbA1c > 6.5%, or requiring treatment with any anti-diabetic medication (e.g. insulin, metformin, etc) within the 2 weeks prior to enrolment.
- Use of any investigational agent in the 4 weeks prior to enrolment, including any anti-cytokine/chemokine agents.
- Pregnant or breast-feeding women; unwillingness to use effective contraceptive measures (females and males). (NB: pregnancy should be avoided in patients or partners during the first month after completing the treatment with the Investigational Product; no other specific warnings are described, considering the treatment course of the Investigational Product, its PK profile, and the lack of significant adverse effects on mating performance and fertility in animal studies).
- Patients with past or current history of alcohol abuse based on clinical history and/or past treatment for alcohol addiction.
- Patients with evidence of pre-operative portal hypertension as per clinical history and abdominal/liver imaging by ultrasound techniques.
Sites will comply with any additional or more restrictive exclusion criteria locally accepted, as per centre practice.
Data sourced from ClinicalTrials.gov (NCT01967888). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.