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

Chronic Pancreatitis Clinical Trial

— Tactic  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02693093
• Other study ID #: NI03-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 24, 2016
• Est. completion date: December 30, 2021

Study information

• Verified date: December 2022
• Source: Kangen Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 264
• Est. completion date: December 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Pancreatitis
• Pancreatitis
• Pancreatitis, Chronic

Intervention

Drug:
• NI-03

• Placebo

Locations

Country	Name	City	State
Russian Federation	Federal Research Centre Institute of Cytology and Genetics	Novosibirsk
Russian Federation	1st Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	City Hospital #40	Saint Petersburg
Russian Federation	City Polyclinic #4	Saint Petersburg
Russian Federation	Military Medical Academu, Dep of Therapy of Adv. Training	Saint Petersburg
Russian Federation	Military Medical Academy, Department of Hospital Therapy	Saint Petersburg
Russian Federation	Medical University "Reaviz"	Samara
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Ukraine	Institute of Gastroenterology	Dnipro
Ukraine	Central city Clinical Hospital, Therapeutic Department #2	Ivano-Frankivsk
Ukraine	City Policlinic #9	Kharkiv
Ukraine	Malaya Therapy National Institute	Kharkiv
Ukraine	City Hospital Named After Tropins, Therapy Department #1	Kherson
Ukraine	Medical Center "Consilium Medical"	Kyiv
Ukraine	OK Clinic	Kyiv
Ukraine	Emergency Care Hospital, #1 Therapeutic Department	Lviv
Ukraine	Regional Hospital, Department of General Surgery	Odesa
Ukraine	1st City Clinical Hospital, Therapeutic Department	Poltava
Ukraine	City Clinical Hospital #1, Gastroenterology Department	Vinnytsia
Ukraine	Medical Centre Diaservis	Zaporizhia
United States	Texas Clinical Research Institute	Arlington	Texas
United States	University of Colorado-Div of Gastroenterology and Hepatology	Aurora	Colorado
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University (OSU) - Wexner Medical Center	Columbus	Ohio
United States	Texas Tech University Health Sciences Center	El Paso	Texas
United States	University of Florida - Division of Gastroenterology	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University - Indiana University Hospital	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Arkansas	Little Rock	Arkansas
United States	Kaiser Permanente Medical Group	Los Angeles	California
United States	University of Southern California, Keck School of Medicine	Los Angeles	California
United States	Wisconsin Center for Advanced Research, a division of GI Associates LLC	Milwaukee	Wisconsin
United States	Gastroenterology Group of Naples	Naples	Florida
United States	Yale School of Medicine	New Haven	Connecticut
United States	Columbia University School of Medicine	New York	New York
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Virginia Mason	Seattle	Washington
United States	Stanford University School of Medicine	Stanford	California
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PMG Research of Winston-Salem	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts
United States	Gastroenterology Associates of Western Michigan	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Kangen Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Phase 2 - Efficacy Analysis - average daily worst pain intensity score		4 Weeks
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Phase 2 - Efficacy Analysis - Change from baseline in least pain score		change from baseline to Week 4
Secondary	Phase 2 - Efficacy Analysis - Change from baseline in average pain score		4 Weeks
Secondary	Phase 2 - Efficacy Analysis - Change from baseline in current pain score		4 Weeks
Secondary	Phase 2 - Efficacy Analysis - Change from baseline in average morphine-equivalent daily opioid daily dose		4 Weeks
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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