A Dose Ranging Study Evaluating Efficacy and Safety of NI-03
- Registration Number
- NCT02693093
- Lead Sponsor
- Kangen Pharmaceuticals, Inc
- Brief Summary
The purpose of this study is to determine the safety and efficacy of NI-03.
- Detailed Description
The primary objective of the Single-Dose Phase is to assess the pharmacokinetics (PK) and safety of single doses of NI-03 when administered at doses of 100 mg, 200 mg or 300 mg to subjects with chronic pancreatitis.
The primary objective of the Double-Blind Phase of the study is to determine the efficacy, PK and safety of three doses of NI-03 (100 mg, 200 mg and 300 mg) as compared to placebo when administered three times daily (TID) for 28 consecutive days in subjects with chronic pancreatitis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 264
To be eligible to participate in this study, subjects must meet all of the following criteria at Screening:
- Males and females aged 18 to 85 years, inclusive, at the time of consent
- Ability to communicate effectively with clinic site staff, ability and willingness to comply with the study schedule, restrictions, and requirements
- Institutional Review Board (IRB)-approved written informed consent
- Diagnosis of chronic pancreatitis
- Baseline average daily worst pain score must be a minimum of 4 using the Numeric Rating Scale (NRS) during the 7-day run-in period
- Patients on a non-opioid analgesic regimen that is expected to remain stable during the study period, or an opioid regimen with a morphine-equivalent dose not more than 100 mg daily.
To be eligible to participate in this study, subjects must not meet any of the following criteria:
- Any other clinically significant medical condition
- Treatment with any investigational product within 14 days of Day 1 (or 5 drug half-lives if 5 drug half-lives are expected to exceed 14 days) of Day -7
- Major abdominal surgery within 90 days of Day 1
- History or presence of clinically significant cardiovascular disease
- History of any cancer, except non-melanoma skin cancer, within 5 years of study enrollment,
- History of endoscopic intervention within the previous 3 months or presence of a pancreatic duct stent
- History of illicit drug abuse (i.e. use of any 'illegal' drugs within 6 months)
- Active heavy alcohol use (defined as more than 2 alcoholic drinks per day or 14 alcoholic drinks per week)
- Inadequate venous access
- Significant blood loss, donation of ≥450 mL of blood, or blood or blood product transfusion within 7 days of Day 1
- History or presence of hepatitis B (surface antigen positivity), active hepatitis C or human immunodeficiency virus (HIV) antibody
- Active infection within 30 days of Day 1
- Pregnant, planning to become pregnant or breast feeding
- Positive urine or serum pregnancy test result at Screening or on Day 1
- Active major psychiatric illness requiring a change in treatment within 3 months that would confound pain assessments
- History of seizures within the last 12 months
- Current use of anticonvulsants, antipsychotics, systemic steroids and, immunosuppressant therapy. *Use of gabapentin, pregabalin and benzodiazepines as treatment for chronic pancreatitis pain are allowed.
- Presence of generalized pain syndrome apart from chronic pancreatitis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo Placebo TID Day for 28 Days 100 mg NI-03 NI-03 TID Day for 28 Days 200 mg NI-03 NI-03 TID Day for 28 Days 300 mg NI-03 NI-03 TID Day for 28 Days
- Primary Outcome Measures
Name Time Method Phase 1 - Safety and Tolerability - Laboratory test results through 7 days post-dose Laboratory test results will be graded and summarized based on CTCAE v4.03. and by shifts in results before and after dosing
Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose Pharmacokinetic (PK) parameters such as Maximum concentration (Cmax), time to maximum concentration (Tmax), minimum concentration(Cmin), area under the curve (AUC), half-life (t1/2), apparent clearance (CL/F), and apparent volume of distribution (Vz/F) are assessed.
Phase 1 - Safety and Tolerability - Treatment Emergent Adverse Events (TEAE) via CTCAE v4.0 through 7 days post-dose Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Phase 2 - Efficacy Analysis - average daily worst pain intensity score 4 Weeks
- Secondary Outcome Measures
Name Time Method Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - plasma terminal half-life (t1/2) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA -area under the curve (AUC) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - Maximum concentration (Cmax) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - time to maximum plasma concentration (tmax) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent clearance (CL/F) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent volume of distribution (Vz/F) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 2 - Efficacy Analysis - Change from baseline in least pain score change from baseline to Week 4 Phase 2 - Efficacy Analysis - Change from baseline in average pain score 4 Weeks Phase 2 - Efficacy Analysis - Change from baseline in current pain score 4 Weeks Phase 2 - Efficacy Analysis - Change from baseline in average morphine-equivalent daily opioid daily dose 4 Weeks Phase 2 - Efficacy Analysis - Change from baseline in quality of life change from baseline to Week 4 assessed using the pain interference aspects of the Brief Pain Inventory (BPI)
Phase 2 - Safety and Tolerability - Treatment Emergent Adverse Events (TEAE) via CTCAE v4.0 Through day 57 (End of Study Visit) Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Phase 2 - Safety and tolerability - Laboratory Test Results Through day 57 (End of Study Visit) Laboratory test results will be graded and summarized based on CTCAE v4.03. and by shifts in results before and after dosing
Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA -area under the curve (AUC) Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - Maximum concentration (Cmax) pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose. Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - time to maximum plasma concentration (tmax) Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - plasma terminal half-life (t1/2) Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent clearance (CL/F) Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent volume of distribution (Vz/F) Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose
Trial Locations
- Locations (48)
Regional Hospital, Department of General Surgery
🇺🇦Odesa, Ukraine
City Clinical Hospital #1, Gastroenterology Department
🇺🇦Vinnytsia, Ukraine
PMG Research of Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
City Hospital Named After Tropins, Therapy Department #1
🇺🇦Kherson, Ukraine
Columbia University School of Medicine
🇺🇸New York, New York, United States
Medical University "Reaviz"
🇷🇺Samara, Russian Federation
Indiana University - Indiana University Hospital
🇺🇸Indianapolis, Indiana, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Gastroenterology Group of Naples
🇺🇸Naples, Florida, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Ohio State University (OSU) - Wexner Medical Center
🇺🇸Columbus, Ohio, United States
UPMC Presbyterian
🇺🇸Pittsburgh, Pennsylvania, United States
Virginia Mason
🇺🇸Seattle, Washington, United States
Central city Clinical Hospital, Therapeutic Department #2
🇺🇦Ivano-Frankivsk, Ukraine
Baylor College of Medicine
🇺🇸Houston, Texas, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Federal Research Centre Institute of Cytology and Genetics
🇷🇺Novosibirsk, Russian Federation
City Polyclinic #4
🇷🇺Saint Petersburg, Russian Federation
1st Saint Petersburg State Medical University
🇷🇺Saint Petersburg, Russian Federation
OK Clinic
🇺🇦Kyiv, Ukraine
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Military Medical Academy, Department of Hospital Therapy
🇷🇺Saint Petersburg, Russian Federation
Tomsk Regional Clinical Hospital
🇷🇺Tomsk, Russian Federation
City Hospital #40
🇷🇺Saint Petersburg, Russian Federation
Malaya Therapy National Institute
🇺🇦Kharkiv, Ukraine
1st City Clinical Hospital, Therapeutic Department
🇺🇦Poltava, Ukraine
University of Arkansas
🇺🇸Little Rock, Arkansas, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Borland-Groover Clinic
🇺🇸Jacksonville, Florida, United States
University of Southern California, Keck School of Medicine
🇺🇸Los Angeles, California, United States
Kaiser Permanente Medical Group
🇺🇸Los Angeles, California, United States
University of Colorado-Div of Gastroenterology and Hepatology
🇺🇸Aurora, Colorado, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Chesterfield, Michigan, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Texas Tech University Health Sciences Center
🇺🇸El Paso, Texas, United States
Military Medical Academu, Dep of Therapy of Adv. Training
🇷🇺Saint Petersburg, Russian Federation
Institute of Gastroenterology
🇺🇦Dnipro, Ukraine
City Policlinic #9
🇺🇦Kharkiv, Ukraine
Emergency Care Hospital, #1 Therapeutic Department
🇺🇦Lviv, Ukraine
Medical Center "Consilium Medical"
🇺🇦Kyiv, Ukraine
Medical Centre Diaservis
🇺🇦Zaporizhia, Ukraine
Gastroenterology Associates of Western Michigan
🇺🇸Wyoming, Michigan, United States
Wisconsin Center for Advanced Research, a division of GI Associates LLC
🇺🇸Milwaukee, Wisconsin, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
University of Florida - Division of Gastroenterology
🇺🇸Gainesville, Florida, United States