Oral Nafamostat in Healthy Volunteers (NAF-101)

NCT04406415 | Completed Phase 1 FDA Drug

• 2 other identifiers: NAF-101UG3DA047682-02
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled Multiple Ascending Dose (MAD) study to evaluate the safety, tolerability and pharmacokinetics of oral nafamostat solution administered t.i.d.. for up to 5 days in healthy volunteer adult subjects

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Number of participants with adverse events including out-of-range clinical laboratory measures, vital signs, ECG, and spontaneous adverse event reports throughout the 14 day study period

  14 Days

Secondary Outcomes (4)

• Pharmacokinetics (Cmax)

  Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5

• Pharmacokinetics (Tmax)

  Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5

• Pharmacokinetics (AUC)

  Pre-dose (0 hr) and at 0.5, 1, 2, 3, 4, 6, and 8 hr after first dose on Day 1 and again after the last dose on Day 5

• Dose Selection

  5 Days

Study Arms (5)

10 mg

EXPERIMENTAL

10 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days

Drug: Nafamostat Mesilate

50 mg

EXPERIMENTAL

50 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days

Drug: Nafamostat Mesilate

100 mg

EXPERIMENTAL

100 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days

Drug: Nafamostat Mesilate

200 mg

EXPERIMENTAL

200 mg nafamostat three times a day (t.i.d., approximately q8h) for up to 5 days

Drug: Nafamostat Mesilate

Placebo

PLACEBO COMPARATOR

Placebo administered three times a day (t.i.d., approximately q8h) for up to 5 days

Drug: Placebo

Interventions

Nafamostat Mesilate DRUG

Oral nafamostat, 10, 50, 100, or 200 mg administered three times daily for up to 5 days

10 mg; 100 mg; 200 mg; 50 mg

Placebo DRUG

Oral placebo administered three times daily for up to 5 days

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, age 18 to 70 years old, able and willing to provide written informed consent to participate in the study;
• Subjects must be in generally good health as determined by pre-study medical history, physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG);
• Subjects must be willing to remain in confinement at the clinical study unit for 6.5 consecutive days and to return to the unit at Day 14±2 for followup safety assessments;
• Body mass index (BMI) 19-32 kg/m2;
• Normal blood pressure (BP) \[systolic BP 90-140 mmHg, diastolic BP 50-90 mmHg\] and heart rate (HR) \[resting HR 45-90 beats per minute (bpm)\] without medication;
• Clinical chemistry profile including electrolytes, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), creatinine, and urea must be within the normal range without medication; screening liver enzymes may be up to 1.5x normal range; screening CPK must be within 2x normal range;
• Urinalysis including urinary creatinine must be within normal limits (trace findings and minor deviations are acceptable per the clinical decision of the Principal Investigator);
• Subjects must be non-smokers or willing to abstain from smoking for the duration of study;
• Subjects must be able to read, understand and follow the study instructions;
• Male subjects and their female sexual partners must agree to use double barrier contraception during the study period and for 2 months afterward, or provide proof of post-menopausal state (minimum 1 year) or surgical sterility.
• Female subjects will be non-pregnant, non-lactating, and either postmenopausal for at least 1 year, or surgically sterile for at least 3 months, or will agree to use double-barrier contraception from 28 days and/or their last confirmed menstrual period prior to study enrollment (whichever is longer) until 2 months after Clinic Discharge. Double barrier contraception may include, but is not limited to, non-hormonal intrauterine device with spermicide, female condom with spermicide, diaphragm with spermicide, cervical cap with spermicide; having a male sexual partner who agrees to use a male condom with spermicide; or having a sterile sexual partner. Females will refrain from using hormonal contraceptives for at least 28 days prior to study entry until the end of the study period (Day 14). For all females, the pregnancy test result must be negative at Screening and Pre-Study Baseline (Days -1 to -10).

You may not qualify if:

• Use of any non-study medication(s) including low dose aspirin for cardiovascular prophylaxis within one week prior and two weeks after receipt of study drug;
• Use of chemotherapy agents or history of cancer, other than non-metastatic skin cancer that has been completely excised, within five years prior to the screening visit;
• History of bacterial or viral infection requiring treatment with antibiotics or antivirals within 1 month of study;
• History of congestive heart failure;
• Use of drugs which are P450 inducers or inhibitors within the past 30 days (e.g. cimetidine, paroxetine, fluoxetine, haloperidol, ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin);
• Use of any dietary aids or foods that are known to modulate drug metabolizing enzymes (e.g. St. John's Wort, grapefruit juice) within 14 days of dose administration;
• History of seizure disorder;
• Serious psychosocial co-morbidities;
• Cognitive or psychiatric disorders, or any other condition that could interfere with compliance with study procedures and/or confinement in a clinical study unit for 6.5 days;
• History of drug or alcohol abuse within one year prior to screening;
• Use of any other investigational drug within 1 month prior to enrollment;
• Use of prescription drugs within 1 month prior to enrollment;
• Use of over the counter medication excluding routine vitamins, but including mega-dose vitamin therapy, within one week of enrollment;
• Donation and/or receipt of any blood or blood products within 3 months prior to enrollment;
• Family history of significant cardiac disease (i.e. sudden death in first degree relative; myocardial infarction prior to 50 years old).

Sponsors & Collaborators

• Ensysce Biosciences: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Arizona Research Center

Phoenix, Arizona, 85023, United States

Location

MeSH Terms

Interventions

nafamostat

Study Officials

• William K Schmidt, PhD

  Ensysce Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a double-blinded study. Subjects will not be informed of their treatment assignment (active or placebo); however, investigators and clinical site staff will have access to the randomization codes.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled, Multiple Ascending Dose (MAD) study with 4 active drug cohorts

Study Record Dates

• First Submitted: May 24, 2020
• First Posted: May 28, 2020
• Study Start: September 21, 2020
• Primary Completion: November 11, 2020
• Study Completion: May 14, 2021
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)