Single Ascending-dose Study to Evaluate Safety, Tolerability, and PK of MYMD1 in Healthy Male Adult Subjects

TNF Pharmaceuticals, Inc.40 enrolled

Overview

Double-blind, placebo-controlled, First-in-Human, single ascending-dose study. Approximately 40 healthy adult male subjects will be given a single capsule of MYMD1 to determine its safety, how well it is tolerated, how the body acts on the experimental drug, and how the experimental drug acts on the body. This will be based on blood and urine sample analysis and other physical measurements.

A single-center, double-blind, placebo-controlled, first-in-human, single ascending-dose study to evaluate the safety, tolerability, and pharmacokinetics of single oral dose capsules of MYMD1 in healthy male adult subjects. Each subject will participate in the study for approximately 7 weeks, including a Screening period of up to 30 days, a confinement period of 4 days, and a follow-up period of approximately 2 weeks. In each cohort, 8 subjects will be administered a single dose of either MYMD1 (N=6 in each cohort) or Placebo (N=2 in each cohort), under fasted conditions, and each subject will participate in only 1 of the 5 cohorts during the study. Anticipated dosing levels will be 5mg (Cohort 1), 10mg (Cohort 2), 15mg (Cohort 3), 20mg (Cohort 4), and 25mg (Cohort 5). Sentinel dosing will be used to initiate each cohort, and the first 2 subjects will be randomized 1:1 to receive either MYMD1 or Placebo. The remaining subjects will be dosed 5:1 to receive either MYMD1 or Placebo, respectively.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Undefined

Interventions

MyMD1DRUG

Isomyosamine 5mg capsules

PlaceboDRUG

Placebo

Eligibility

Sex: MALEMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Written Informed Consent. * Stable medical history and general health. * Body weight between 60 - 100 kg and Body Mass Index (BMI) of 18-31 kg/m2. * Estimated GFR (eGFR) - mL/min/1.73m2 or estimated creatinine clearance (CLcr) (mL) ≥90. * Normal hepatic function. * Adequate peripheral venous access. * Test negative for HIV, hepatitis C virus antibodies, and hepatitis B surface antigen (HBsAg). * Test negative for drugs of abuse. * Willing and able to complete all study assessments and procedures and to communicate effectively with the Investigator and study center staff. * Willing to use effective contraception from Day -1 until 90 days after receiving study medication. Exclusion Criteria: * Allergy to any product ingredients. * Unable to swallow capsules. * Elective medical procedure during study. * Abusing drugs or alcohol and/or history of drug or alcohol dependence within 6 months of study entry. * History of seizure disorder requiring medical treatment after 18 years of age. * Current smoker or smokeless tobacco user. * Participation in drug or medical device clinical study within 30 days of study. entry or 5 times half-life of study drug, whichever is longer. * Medically significant standard clinical laboratory assessments. * Significant medical condition which might interfere with the study or put subject at significant risk. * QTcF \>450 ms or clinically significant ECG abnormalities. * Elevation of blood pressure (BP) - Supine BP \>145mmHg; Diastolic BP. \>92mmHg;l heart rate (HR) \>100 bpm. * Gastrointestinal malabsorption. * Abnormal thyroid function (TSH, T4 and/or T3 levels): elevated thyroid antibodies (anti- TPO and/or anti-Thyroglobulin); thyroid goiter, or known thyroid nodule(s) at Baseline; \>Abnormal renal function (estimated GFR \>90mL/min/1.73m2 or estimated creatinine clearance \<90mL) and/or abnormal hepatic function at Baseline. * Treatment with any prescription or nonprescription drugs, including vitamins, minerals, or herbal and dietary supplements, within 14 days or 5 half-lives of Day 1, whichever is longer - except Tylenol. * Use within 30 days prior to Day 1 of any drugs or substances, including grapefruit juice, that are known to strongly inhibit or induce cytochrome P450 (CYP) enzymes. * Donation of blood or blood product within 56 days of Day 1.

Locations (1)

Palm Beach CRO, LLC

West Palm Beach, Florida, United States

Outcomes

Primary Outcomes

Adverse Events

Any untoward medical occurrence in a subject which does not necessarily have a causal relationship with this treatment. Assessed as number and percent of patients with adverse events, compared across treatment and Placebo groups .

Time frame: 5 days

Changes in Physical examination: Neurologic Systems

Neurologic systems, including testing of patellar reflex using rubber mallet. Assessed by Investigator, based on education, experience, and training, as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms". Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Variation of MyMD1 concentration in blood plasma as a function of time

AUC (0-inf)

Time frame: 5 days

Change from Baseline QTcF and QTcB

Derived from centrally-overread 12-lead ECGs, measured in triplicate, based on Holter monitoring. Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Serum Chemistry: BUN, Creatinine, Glucose, Magnesium, Cholesterol, Calcium, Uric Acid, C-Reactive Protein, Total Bilirubin, Direct Bilirubin, Phosphate, and Triglycerides.

Number of patients with clinically significant changes from Baseline in Blood Urea Nitrogen (BUN); Creatinine; Glucose (fasting); Magnesium; Cholesterol; Calcium; Uric Acid; C-Reactive Protein; Total Bilirubin; Direct Bilirubin; Phosphate; and Triglycerides, compared across treatment and Placebo groups. All tests measured in mg/dL.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: BUN, Creatinine, Glucose, Magnesium, Cholesterol, Calcium, Uric Acid, C-Reactive Protein, Total Bilirubin, Direct Bilirubin, Phosphate, and Triglycerides.

Data from ClinicalTrials.gov

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Percentage of patients with clinically significant changes from Baseline in Blood Urea Nitrogen (BUN); Creatinine; Glucose (fasting); Magnesium; Cholesterol; Calcium; Uric Acid; C-Reactive Protein; Total Bilirubin; Direct Bilirubin; Phosphate; and Triglycerides, compared across treatment and Placebo groups. All tests measured in mg/dL.

Number of Patients with Changes in clinical laboratory values - Serum Chemistry: albumin, globulin, Total protein.

Number of patients with clinically significant changes from Baseline in albumin, globulin, and total protein, compared across treatment and Placebo groups. All tests measured in g/dL.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: albumin, globulin, Total protein.

Percentage of patients with clinically significant changes from Baseline in albumin, globulin, and total protein, compared across treatment and Placebo groups. All tests measured in g/dL.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Serum Chemistry: Electrolytes

Number of patients with clinically significant changes from Baseline in Potassium, Sodium, Chloride, and Carbon Dioxide (bicarbonate), compared across treatment and Placebo groups. All tests measured in mmol/L.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: Electrolytes

Percentage of patients with clinically significant changes from Baseline in Potassium, Sodium, Chloride, and Carbon Dioxide (bicarbonate), compared across treatment and Placebo groups. All tests measured in mmol/L.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Serum Chemistry: Creatine Kinase muscle/brain (MB) fraction

Number of patients with clinically significant changes from Baseline in Creatine Kinase muscle/brain (MB) fraction, compared across treatment and Placebo groups. All tests measured in ng/mL.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: Creatine Kinase muscle/brain (MB) fraction

Percentage of patients with clinically significant changes from Baseline in Creatine Kinase muscle/brain (MB) fraction, compared across treatment and Placebo groups. All tests measured in ng/mL.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Serum Chemistry: Gamma Glutamyl Transferase, Lactate dehydrogenase, Aspartate Aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Creatine kinase, and Amylase

Number of patients with clinically significant changes from Baseline in Gamma Glutamyl Transferase, Lactate dehydrogenase, Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT), Alkaline phosphatase, Creatine kinase, and Amylase,compared across treatment and Placebo groups. All tests measured in U/L.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: Gamma Glutamyl Transferase, Lactate dehydrogenase, Aspartate Aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Creatine kinase, and Amylase

Percentage of patients with clinically significant changes from Baseline in Gamma Glutamyl Transferase, Lactate dehydrogenase, Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT), Alkaline phosphatase, Creatine kinase, and Amylase,compared across treatment and Placebo groups. All tests measured in U/L.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Hematology:Red Blood Cell count

Number of patients with clinically significant changes from Baseline in Red Blood Cell count, compared across treatment and Placebo groups. All tests measured in Millions/microL.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Hematology:Red Blood Cell count

Percentage of patients with clinically significant changes from Baseline in Red Blood Cell count, compared across treatment and Placebo groups. All tests measured in Millions/microL.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Hematology: Platelet count, White Blood Cell count

Number of patients with clinically significant changes from Baseline in Platelet count and White Blood Cell count, compared across treatment and Placebo groups. All tests measured in Thousands/microL.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Hematology: Platelet count, White Blood Cell count

Percentage of patients with clinically significant changes from Baseline in Platelet count and White Blood Cell count, compared across treatment and Placebo groups. All tests measured in Thousands/microL.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Hematology: Hematocrit, Reticulocytes

Number of patients with clinically significant changes from Baseline in hematocrit and reticulocytes, compared across treatment and Placebo groups. All tests measured in %.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Hematology: Hematocrit, Reticulocytes

Percentage of patients with clinically significant changes from Baseline in hematocrit and reticulocytes, compared across treatment and Placebo groups. All tests measured in %.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular volume, Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils

Number of patients with clinically significant changes from Baseline in Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils, compared across treatment and Placebo groups. All tests measured in cells/microL.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular volume, Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils

Percentage of patients with clinically significant changes from Baseline in Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils, compared across treatment and Placebo groups. All tests measured in cells/microL.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular hemoglobin

Number of patients with clinically significant changes from Baseline in Mean corpuscular hemoglobin, compared across treatment and Placebo groups. All tests measured in pg.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular hemoglobin

Percentage of patients with clinically significant changes from Baseline in Mean corpuscular hemoglobin, compared across treatment and Placebo groups. All tests measured in pg.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - coagulation: Fibrinogen

Number of patients with clinically significant changes from Baseline in fibrinogen (mg/dL), compared across treatment and Placebo groups.

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - coagulation: Fibrinogen

Percentage of patients with clinically significant changes from Baseline in fibrinogen (mg/dL), compared across treatment and Placebo groups.

Time frame: 5 days

Number of Patients with Changes in clinical laboratory values - coagulation: Prothrombin time, Activated partial thromboplastin time, Thrombin time

Number of patients with clinically significant changes from Baseline time, Activated partial thromboplastin time, Thrombin time compared across treatment and Placebo groups. All tests measured in seconds (sec).

Time frame: 5 days

Percentage of Patients with Changes in clinical laboratory values - coagulation: Prothrombin time, Activated partial thromboplastin time, Thrombin time

Percentage of patients with clinically significant changes from Baseline time, Activated partial thromboplastin time, Thrombin time compared across treatment and Placebo groups. All tests measured in seconds (sec).

Time frame: 5 days

Changes in Physical examination: Cardiovascular

Assessed by Investigator, based on education, training, and experience, using stethoscope, as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms". Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Physical examination: Head, eye, ear, nose, and throat

Otolaryngologic head, eye, ear, nose, and throat exam, based on Investigator observation, based on experience, education, and training. Visual assessment of clinical appearance. Ear examined using a flashlight. Throat examined using a tongue depressor. Assessed by Investigator as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms". Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Electrocardiogram (ECG): Heart Rate

12-lead; Number of patients with clinically significant changes from Baseline in Electrocardiogram (ECG) measures of Heart Rate (beats per minute - bpm). Assessed by Investigator as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms"

Time frame: 5 days

Changes in Electrocardiogram (ECG): PR, RR, QRS, QT, QTcF, and QTcB

12-lead. Number of patients with changes from Baseline in PR Interval (ms); RR Intermal (ms); QRS Interval (ms); QT Interval (ms); QTcF Interval (ms); and QTcB Interval (ms)

Time frame: Time of Assessment (24-Hour Clock)

Vital signs: Oral Temperature (degrees Centigrade)

Oral temperature, using oral thermometer. Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Physical examination: General Appearance

Physical signs and symptoms assessed by Investigator observation, based on experience, education, and training. May include observation of obesity or dermatologic conditions. Assessed by Investigator as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms". Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Physical examination: Respiratory

Respiratory, measured in breaths per minute (bpm) Assessed by Investigator, based on education, experience, and training, as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms". Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Physical examination: Gastrointestinal

Gastrointestinal signs and symptoms. May include evaluation of normal bowel movements or abdominal pain. Assessed by Investigator, based on education, experience, and training, as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms". Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Physical examination: Body Weight

Body Weight measured in kg using scale. Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Changes in Physical examination: Height

Height (cm) measured using ruler attached to weighing scale.

Time frame: 5 days

Pharmacokinetics: AUC

Area Under the Curve (AUC) (0-last): variation of a drug concentration in blood plasma as a function of time

Time frame: 5 days

Pharmacokinetics: Cmax

Cmax - Maximum Concentration of drug substance in blood plasma

Time frame: 5 days

Pharmacokinetics: tmax

tmax - Time to Maximum Concentration of drug substance in blood plasma

Time frame: 5 days

Pharmacokinetics: t 1/2

Time to metabolism of 1/2 of dose (eg, half-life) of drug substance in blood plasma

Time frame: 5 days

Pharmacokinetics: CL/F

Oral Clearance of the drug substance (CL/F)

Time frame: 5 days

Pharmacokinetics: V2/F

V2/F

Time frame: 5 days

Vital Signs: Pulse Rate

pulse rate measured in beats per minute (bpm). Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Vital signs: Blood Pressure

Sitting diastolic and systolic blood pressure, measured by Karotkoff Cuff in mmHg. Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Vital signs: Respiratory Rate

Respiratory rate, measured in breaths per minute. Assessed as number and percent of patients with clinically significant changes from Baseline, compared across treatment and Placebo groups.

Time frame: 5 days

Thyroid Test: Trilodothyronine (Free T3)

Number and percent of patients with clinically significant changes from Baseline in Free T3 (pg/mL), compared across treatment and Placebo groups.

Time frame: 5 days

Thyroid Test: Thyroxine (Free T4)

Number and percent of patients with clinically significant changes from Baseline in Free T4 (ng/dL), compared across treatment and Placebo groups.

Time frame: 5 days

Thyroid Test: Thyroid Stimulating Hormone (TSH)

Number and percent of patients with clinically significant changes from Baseline in TSH (mIU/L), compared across treatment and Placebo groups.

Time frame: 5 days

Urinalysis: Urobilinogen

Number and percent of patients with clinically significant changes from Baseline in Urobilinogen (eu/dL), compared across treatment and Placebo groups.

Time frame: 5 days

Urinalysis (Microscopic)

Number and percent of patients with clinically significant changes from Baseline in Red Blood Cell (RBC), Epithelial Cells, Bacteria, Casts, and White Blood Cell (WBC) counts, compared across treatment and Placebo groups. All units measured as /lpf.

Time frame: 5 days