Clinical trial NCT02693093: A Dose Ranging Study Evaluating Efficacy and Safety of NI-03
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Pancreatitis
Lead sponsor: Kangen Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2016-02-26
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose
measure: Phase 1 - Safety and Tolerability - Treatment Emergent Adverse Events (TEAE) via CTCAE v4.0
timeFrame: through 7 days post-dose
measure: Phase 1 - Safety and Tolerability - Laboratory test results
timeFrame: through 7 days post-dose
measure: Phase 2 - Efficacy Analysis - average daily worst pain intensity score
timeFrame: 4 Weeks
Secondary outcomes:
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA -area under the curve (AUC)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - Maximum concentration (Cmax)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - time to maximum plasma concentration (tmax)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent clearance (CL/F)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - plasma terminal half-life (t1/2)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 1 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent volume of distribution (Vz/F)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 2 - Efficacy Analysis - Change from baseline in least pain score
timeFrame: change from baseline to Week 4
measure: Phase 2 - Efficacy Analysis - Change from baseline in average pain score
timeFrame: 4 Weeks
measure: Phase 2 - Efficacy Analysis - Change from baseline in current pain score
timeFrame: 4 Weeks
measure: Phase 2 - Efficacy Analysis - Change from baseline in average morphine-equivalent daily opioid daily dose
timeFrame: 4 Weeks
measure: Phase 2 - Efficacy Analysis - Change from baseline in quality of life
timeFrame: change from baseline to Week 4
measure: Phase 2 - Safety and Tolerability - Treatment Emergent Adverse Events (TEAE) via CTCAE v4.0
timeFrame: Through day 57 (End of Study Visit)
measure: Phase 2 - Safety and tolerability - Laboratory Test Results
timeFrame: Through day 57 (End of Study Visit)
measure: Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA -area under the curve (AUC)
timeFrame: Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose
measure: Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - Maximum concentration (Cmax)
timeFrame: pre-dose and at 0.25, 0.5, 1, 2, 4 and 8 hours post-dose.
measure: Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - time to maximum plasma concentration (tmax)
timeFrame: Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose
measure: Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - plasma terminal half-life (t1/2)
timeFrame: Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose
measure: Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent clearance (CL/F)
timeFrame: Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose
measure: Phase 2 - To determine the pharmacokinetic profile for FOY251 and GBA - apparent volume of distribution (Vz/F)
timeFrame: Days 1 and 29, and at 0.25, 0.5, 1, 2 and 4 hours post-dose
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Los Angeles
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: Los Angeles
country: United States
facility: University of Southern California, Keck School of Medicine
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado-Div of Gastroenterology and Hepatology
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida - Division of Gastroenterology
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples
state: Florida
city: Urbana
country: United States
facility: The Carle Foundation Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University - Indiana University Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University School of Medicine
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University (OSU) - Wexner Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Virginia Mason
state: Washington
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research, a division of GI Associates LLC
state: Wisconsin
city: Novosibirsk
country: Russian Federation
facility: Federal Research Centre Institute of Cytology and Genetics
city: Saint Petersburg
country: Russian Federation
facility: Military Medical Academu, Dep of Therapy of Adv. Training
city: Saint Petersburg
country: Russian Federation
facility: Military Medical Academy, Department of Hospital Therapy
city: Saint Petersburg
country: Russian Federation
facility: 1st Saint Petersburg State Medical University
city: Saint Petersburg
country: Russian Federation
facility: City Hospital #40
city: Saint Petersburg
country: Russian Federation
facility: City Polyclinic #4
city: Samara
country: Russian Federation
facility: Medical University "Reaviz"
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Clinical Hospital
city: Dnipro
country: Ukraine
facility: Institute of Gastroenterology
city: Ivano-Frankivsk
country: Ukraine
facility: Central city Clinical Hospital, Therapeutic Department #2
city: Kharkiv
country: Ukraine
facility: Malaya Therapy National Institute
city: Kharkiv
country: Ukraine
facility: City Policlinic #9
city: Kherson
country: Ukraine
facility: City Hospital Named After Tropins, Therapy Department #1
city: Kyiv
country: Ukraine
facility: OK Clinic
city: Kyiv
country: Ukraine
facility: Medical Center "Consilium Medical"
city: Lviv
country: Ukraine
facility: Emergency Care Hospital, #1 Therapeutic Department
city: Odesa
country: Ukraine
facility: Regional Hospital, Department of General Surgery
city: Poltava
country: Ukraine
facility: 1st City Clinical Hospital, Therapeutic Department
city: Vinnytsia
country: Ukraine
facility: City Clinical Hospital #1, Gastroenterology Department
city: Zaporizhia
country: Ukraine
facility: Medical Centre Diaservis
Study officials:
affiliation: OSU
name: Phiip Hart, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.