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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Undefined

Intervention / Treatment
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* Drug: MyMD1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled, single ascending dose study.
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune, Pharmacokinetics, Phase I, First-in-Human, Safety, Tolerability, Hashimoto thyroiditis