A Dose Ranging Study Evaluating Efficacy and Safety of NI-03 (Tactic)

A Phase 1, Single Dose PK and Safety Study With NI-03 Followed by a Phase 2, Randomized, Double-Blind, Parallel-Group Dose-Ranging Study to Evaluate the Safety and Efficacy of NI-03 When Compared to Placebo in Subjects With Chronic Pancreatitis

The purpose of this study is to determine the safety and efficacy of NI-03.

Study Overview

• Status: Completed
• Conditions: Chronic Pancreatitis
• Intervention / Treatment: Drug: Placebo; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630089
    • Federal Research Centre Institute of Cytology and Genetics
  • Saint Petersburg, Russian Federation, 191015
    • Military Medical Academu, Dep of Therapy of Adv. Training
  • Saint Petersburg, Russian Federation, 191124
    • Military Medical Academy, Department of Hospital Therapy
  • Saint Petersburg, Russian Federation, 197022
    • 1st Saint Petersburg State Medical University
  • Saint Petersburg, Russian Federation, 197706
    • City hospital #40
  • Saint Petersburg, Russian Federation, 199178
    • City Polyclinic #4
  • Samara, Russian Federation, 443011
    • Medical University "Reaviz"
  • Tomsk, Russian Federation, 634063
    • Tomsk Regional Clinical Hospital
• Ukraine
  • Dnipro, Ukraine, 49074
    • Institute of Gastroenterology
  • Ivano-Frankivsk, Ukraine, 76018
    • Central city Clinical Hospital, Therapeutic Department #2
  • Kharkiv, Ukraine, 61039
    • Malaya Therapy National Institute
  • Kharkiv, Ukraine, 61172
    • City policlinic #9
  • Kherson, Ukraine, 73000
    • City Hospital Named After Tropins, Therapy Department #1
  • Kyiv, Ukraine, 02091
    • OK Clinic
  • Kyiv, Ukraine, 04050
    • Medical Center "Consilium Medical"
  • Lviv, Ukraine, 79059
    • Emergency Care Hospital, #1 Therapeutic Department
  • Odesa, Ukraine, 65025
    • Regional Hospital, Department of General Surgery
  • Poltava, Ukraine, 36038
    • 1st City Clinical Hospital, Therapeutic Department
  • Vinnytsia, Ukraine, 21029
    • City Clinical Hospital #1, Gastroenterology Department
  • Zaporizhia, Ukraine, 69076
    • Medical Centre Diaservis
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • University of Arkansas
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Medical Group
    • Los Angeles, California, United States, 90033
      • University of Southern California, Keck School of Medicine
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado-Div of Gastroenterology and Hepatology
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School Of Medicine
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida - Division of Gastroenterology
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Naples, Florida, United States, 34102
      • Gastroenterology Group of Naples
  • Illinois
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5149
      • Indiana University - Indiana University Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • UMASS Memorial Medical Center
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10027
      • Columbia University School of Medicine
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University (OSU) - Wexner Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-2536
      • UPMC Presbyterian
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research, a division of GI Associates LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To be eligible to participate in this study, subjects must meet all of the following criteria at Screening:

1. Males and females aged 18 to 85 years, inclusive, at the time of consent
2. Ability to communicate effectively with clinic site staff, ability and willingness to comply with the study schedule, restrictions, and requirements
3. Institutional Review Board (IRB)-approved written informed consent
4. Diagnosis of chronic pancreatitis
5. 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
6. 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.

Exclusion Criteria:

To be eligible to participate in this study, subjects must not meet any of the following criteria:

1. Any other clinically significant medical condition
2. 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
3. Major abdominal surgery within 90 days of Day 1
4. History or presence of clinically significant cardiovascular disease
5. History of any cancer, except non-melanoma skin cancer, within 5 years of study enrollment,
6. History of endoscopic intervention within the previous 3 months or presence of a pancreatic duct stent
7. History of illicit drug abuse (i.e. use of any 'illegal' drugs within 6 months)
8. Active heavy alcohol use (defined as more than 2 alcoholic drinks per day or 14 alcoholic drinks per week)
9. Inadequate venous access
10. Significant blood loss, donation of ≥450 mL of blood, or blood or blood product transfusion within 7 days of Day 1
11. History or presence of hepatitis B (surface antigen positivity), active hepatitis C or human immunodeficiency virus (HIV) antibody
12. Active infection within 30 days of Day 1
13. Pregnant, planning to become pregnant or breast feeding
14. Positive urine or serum pregnancy test result at Screening or on Day 1
15. Active major psychiatric illness requiring a change in treatment within 3 months that would confound pain assessments
16. History of seizures within the last 12 months
17. Current use of anticonvulsants, antipsychotics, systemic steroids and, immunosuppressant therapy. *Use of gabapentin, pregabalin and benzodiazepines as treatment for chronic pancreatitis pain are allowed.
18. Presence of generalized pain syndrome apart from chronic pancreatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; TID Day for 28 Days	Drug: Placebo
Experimental: 100 mg NI-03; TID Day for 28 Days	Drug: NI-03
Experimental: 200 mg NI-03; TID Day for 28 Days	Drug: NI-03
Experimental: 300 mg NI-03; TID Day for 28 Days	Drug: NI-03

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA	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.	pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose
Phase 1 - Safety and Tolerability - Treatment Emergent Adverse Events (TEAE) via CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	through 7 days post-dose
Phase 1 - Safety and Tolerability - Laboratory test results	Laboratory test results will be graded and summarized based on CTCAE v4.03. and by shifts in results before and after dosing	through 7 days post-dose
Phase 2 - Efficacy Analysis - average daily worst pain intensity score		4 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 - 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 - 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	assessed using the pain interference aspects of the Brief Pain Inventory (BPI)	change from baseline to Week 4
Phase 2 - Safety and Tolerability - Treatment Emergent Adverse Events (TEAE) via CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Through day 57 (End of Study Visit)
Phase 2 - Safety and tolerability - Laboratory Test Results	Laboratory test results will be graded and summarized based on CTCAE v4.03. and by shifts in results before and after dosing	Through day 57 (End of Study Visit)
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

Collaborators and Investigators

• Sponsor: Kangen Pharmaceuticals, Inc
• Investigators: Principal Investigator: Phiip Hart, MD, OSU

Publications and helpful links

General Publications

• Ramsey ML, Nuttall J, Hart PA; TACTIC Investigative Team. A phase 1/2 trial to evaluate the pharmacokinetics, safety, and efficacy of NI-03 in patients with chronic pancreatitis: study protocol for a randomized controlled trial on the assessment of camostat treatment in chronic pancreatitis (TACTIC). Trials. 2019 Aug 14;20(1):501. doi: 10.1186/s13063-019-3606-y.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2016
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (Estimate): February 26, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic
• Other Study ID Numbers: NI03-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No