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

A Double-blind, Placebo-controlled, Randomized, First-in-human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Oral Dose of MYMD1 Capsules in Healthy Male Adult Subjects

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.

Study Overview

• Status: Completed
• Conditions: Undefined
• Intervention / Treatment: Drug: Placebo; Drug: MyMD1

Detailed Description

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
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach CRO, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - 5mg MyMD1; 8 subjects randomized to receive either 5mg MyMD1 (6 subjects) or Placebo (2 subjects)	Drug: Placebo; Placebo; Drug: MyMD1; Isomyosamine 5mg capsules
Experimental: Cohort 2 - 10mg MyMD1; 8 subjects randomized to receive either 10mg MyMD1 (6 subjects) or Placebo (2 subjects)	Drug: Placebo; Placebo; Drug: MyMD1; Isomyosamine 5mg capsules
Experimental: Cohort 3 - 15mg MyMD1; 8 subjects randomized to receive either 15mg MyMD1 (6 subjects) or Placebo (2 subjects)	Drug: Placebo; Placebo; Drug: MyMD1; Isomyosamine 5mg capsules
Experimental: Cohort 4 - 20mg MyMD1; 8 subjects randomized to receive either 20mg MyMD1 (6 subjects) or Placebo (2 subjects)	Drug: Placebo; Placebo; Drug: MyMD1; Isomyosamine 5mg capsules
Experimental: Cohort 5 - 25mg MyMD1 or Placebo; 8 subjects randomized to receive either 25mg MyMD1 (6 subjects) or Placebo (2 subjects)	Drug: Placebo; Placebo; Drug: MyMD1; Isomyosamine 5mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 .	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.	5 days
Variation of MyMD1 concentration in blood plasma as a function of time	AUC (0-inf)	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.	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.	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.	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.	5 days
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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 %.	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 %.	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.	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.	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.	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.	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.	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.	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).	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).	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.	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.	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"	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 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.	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.	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.	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.	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.	5 days
Changes in Physical examination: Height	Height (cm) measured using ruler attached to weighing scale.	5 days
Pharmacokinetics: AUC	Area Under the Curve (AUC) (0-last): variation of a drug concentration in blood plasma as a function of time	5 days
Pharmacokinetics: Cmax	Cmax - Maximum Concentration of drug substance in blood plasma	5 days
Pharmacokinetics: tmax	tmax - Time to Maximum Concentration of drug substance in blood plasma	5 days
Pharmacokinetics: t 1/2	Time to metabolism of 1/2 of dose (eg, half-life) of drug substance in blood plasma	5 days
Pharmacokinetics: CL/F	Oral Clearance of the drug substance (CL/F)	5 days
Pharmacokinetics: V2/F	V2/F	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.	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.	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.	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.	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.	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.	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.	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.	5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker assessment: TNF alpha	Tissue Necrosis Factor (TNF) alpha	5 days
Biomarker assessment: thyroglobulin	thyroglobulin (IU/mL)	5 days
Biomarker assessment: TPO antibodies	thyroperoxidase (TPO) antibodies	5 days
Biomarker assessment	pyridyloxobutyl (POB) adducts in hemophilia	5 days

Collaborators and Investigators

• Sponsor: MyMD Pharmaceuticals, Inc.
• Investigators: Study Director: Art Simon, PhD, Palm Beach CRO, LLC; Principal Investigator: Leonard J Dunn, MD, Clinical Research of West Florida

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2019
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): December 30, 2019

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2020
• Last Update Submitted That Met QC Criteria: April 15, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Safety; First-in-Human; Pharmacokinetics; Phase I; Tolerability; Autoimmune; Hashimoto thyroiditis
• Other Study ID Numbers: MyMD-PK-001

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No