Single Ascending and Multiple Dose Study to Evaluate Safety, Tolerability, and PK of MYMD1 in Healthy Male and Female Adult Subjects

Hashimoto Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05077865
• Other study ID #: MyMD-PK-002
• Status: Completed
• Phase: Phase 1
• Start date: April 26, 2021
• Est. completion date: August 1, 2021

Study information

• Verified date: March 2023
• Source: MyMD Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Double-blind, placebo-controlled, single ascending and multiple dose study. Approximately 32 healthy adult male and female subjects will be given a single capsule of MYMD1 to determine its safety, tolerability, and pharmacokinetic properties. The study data will guide the establishment of an optimum therapeutic dose.

Description:

A single-center, double-blind, placebo-controlled, single ascending and multiple-dose study to evaluate the safety, tolerability, and pharmacokinetics of a single oral dose of MYMD1 capsule in healthy male and female adult subjects. Each subject will participate in the study for approximately 7-8 weeks, including a Screening period of up to 30 days, a confinement period of 2 or 5 days, and a follow-up period of approximately 5 days. In each of Cohorts 1-3, 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. Subjects in Cohort 4 will be administered either MYMD1 (N=6) or Placebo (N=2) on Days 1, 2, 3, 4, and 5. Each subject will participate in only 1 of the 4 cohorts during the study. Anticipated dosing levels will be 150mg (Cohort 1); 300mg (Cohort 2); 250mg (Cohort 3); and 600mg (Cohort 4).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 1, 2021
• Est. primary completion date: August 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Provide written ICF.

2. Is a male or female aged 18 to 65 years.

3. Have a stable medical history and general health as judged by the Investigator on the basis of physical examination, medical history, ECG, and the results of clinical laboratory (chemistry,hematology, coagulation, and urinalysis) testing performed at Screening.

4. Body mass index of 18 to 31 kg/m2, inclusive.

5. Have estimated glomerular filtration rate (mL/min/1.73m2) or estimated creatinine clearance =90 mL.

6. Have normal hepatic function (alanine aminotransferase: 10 to 35 U/L, aspartate aminotransferase: 9 to 46 U/L, total protein: 6.1 to 8.1 g/dL, alkaline phosphatase: 40 to 115 U/L, direct bilirubin: <0.2 mg/dL, and total bilirubin: 0.2 to 1.2 mg/dL).

7. Have adequate peripheral venous access.

8. Test negative for human immunodeficiency virus, hepatitis C virus antibodies, and hepatitis B surface antigen.

9. Test negative for drugs of abuse, including oxycodone, tricyclic anti-depressants, methadone, opiates, marijuana, phencyclidines, barbiturates, methamphetamine, ecstasy, amphetamine, cocaine, and benzodiazepine.

10. Be willing and able to complete all study assessments and procedures and to communicate effectively with the Investigator and study center staff.

11. Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception -

Exclusion Criteria:

1. Have an allergy to any of the study treatment ingredients.

2. Are unable to swallow capsules.

3. Have an elective medical procedure scheduled during the study. Bariatric surgery is also excluded.

4. Currently abusing drugs or alcohol, and/or have a history of drug or alcohol dependence within 6 months of entering this study.

5. Have any history of seizure disorder that has required medical treatment after 18 years of age.

6. Current smoker or smokeless tobacco user, ie, no use of tobacco within 30 days of study entry.

7. Have participated in any drug or medical device-related clinical study within 30 days of study entry.

8. Have values on standard clinical laboratory assessments that are deemed medically significant (show evidence of untreated significant medical illness or pose a risk of significant intercurrent illness during the study in the opinion of the Investigator).

9. Have any significant medical condition that could in the Investigator's opinion interfere with the study or put the subject at a significant risk. These may include, but not limited to the following: active malignant disease, current use of immune-suppressing drugs, currently taking opioid pain medication, and active seizure disorder.

10. On ECG, QTcF >450 ms or the presence of clinically significant abnormalities as determined by the Investigator (Screening or Day -1).

11. Elevation of BP, ie, supine systolic BP >145 mmHg and/or diastolic BP >92 mmHg, or heart rate >100 beats per minute at rest (Screening or Day -1). Readings that fall outside these ranges will be allowed to enter the study if they are health candidates at the Investigator's discretion.

12. Have gastrointestinal malabsorption.

13. Have abnormal renal function (defined as estimated glomerular filtration rate <90 mL/min/1.73m2 or estimated creatinine clearance <90 mL) and/or abnormal hepatic function at baseline.

14. 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.

15. 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. If there is any question as to whether or a not a substance is permitted, please review the product labeling (if applicable) and consult the Sponsor.

16. Donation of blood or any blood product within 56 days of Day 1.

17. Willing to use effective contraception as in from Day -1 until 90 days after receiving study treatment.

18. Once it is confirmed that the subject meets eligibility for check-in, the subject will return approximately 5 to 7 days prior to their scheduled Day -1 to complete a COVID-19 test. All subjects will be required to have a negative test prior to check-in. A positive test will result in exclusion from the study.

Related Conditions & MeSH terms

• Hashimoto Disease

Intervention

Drug:
• MYMD-1
150 mg capsule
• Placebo
Matching in appearance to MyMD-1 150mg capsule

Locations

Country	Name	City	State
United States	Clinical Research of West Florida, Inc	Clearwater	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MyMD Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Any untoward occurrence in a subject which does not necessarily have a causal relationship with this treatment. Assessed as number and percent of subjects with adverse events, compared across treatment and placebo groups.	Cohorts 1,2,3: Continuous through 13 days (includes 10 days post-discharge); Cohort 4: Continuous through 16 days (includes 10 days post-discharge)
Primary	Number of subjects with changes in clinical laboratory values - Serum Chemistry: BUN, Creatinine, Glucose, Magnesium, Cholesterol, Calcium, Uric Acid, C-Reactive Protein, T Bili, D Bili, Phosphate, and Triglycerides.	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Serum Chemistry: Electrolytes	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Serum Chemistry: Creatine Kinase muscle/brain (MB) fraction	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Serum Chemistry: Gamma Glutamyl Transferase (GTT), Lactate dehydrogenase, Aspartate Aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Creatine kinase, and Amylase	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of Subjects with changes in clinical laboratory values - Hematology: Red Blood Cell (RBC) count	Number of subjects with clinically significant changes from Baseline in Red Blood Cell (RBC) count, compared across treatment and Placebo groups.; All tests measured in Millions/microL.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Hematology: Platelet count, White Blood Cell count	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Hematology: Hematocrit, Reticulocytes	Number of subjects with clinically significant changes from Baseline in hematocrit and reticulocytes, compared across treatment and Placebo groups.; All tests measured in %.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Hematology: Mean corpuscular volume, Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils	Number of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - Hematology: Mean corpuscular hemoglobin	Number of subjects with clinically significant changes from Baseline in Mean corpuscular hemoglobin, compared across treatment and Placebo groups.; All tests measured in pg.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - coagulation: Fibrinogen	Number of subjects with clinically significant changes from Baseline in fibrinogen (mg/dL), compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Number of subjects with changes in clinical laboratory values - coagulation: Prothrombin time, Activated partial thromboplastin time, Thrombin time	Number of subjects 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).	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Urinalysis: Microscopic	Number and percent of subjects 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.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Urinalysis: Urobilinogen	Number and percent of subjects with clinically significant changes from Baseline in Urobilinogen (eu/dL), compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Days 2 and 8; Cohort 4: Days 2, 4, 5, 6, & 8.
Primary	Changes in Electrocardiogram (ECG): Heart Rate	Number of subjects with clinically significant changes from Baseline in Electrocardiogram (12-lead ECG) measures of Heart Rate (beats per minute - bpm). Assessed by Investigator as "Normal" or "Abnormal - Clinical Symptoms" or "Abnormal - No Clinical Symptoms"	Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
Primary	Changes in Electrocardiogram (ECG): PR, RR, QRS, QT, QTcF, and QTcB	12-lead. Number of subjects with changes from Baseline Elecrocardiogram (12-lead ECG) measures of PR Interval (ms); RR Interval (ms); QRS Interval (ms); QT Interval (ms); QTcF Interval (ms); and QTcB Interval (ms)	Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
Primary	Change from Baseline QTcF and QTcB	Clinically meaningful changes in cardiac rhythm pertaining to QT interval, derived from centrally-overread 12-lead ECGs, measured in triplicate, based on Holter monitoring. Assessed as number and percent of subjects with clinically significant changes from Baseline, compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.
Primary	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.	Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
Primary	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.	Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
Primary	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 subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
Primary	Changes in Physical examination: Respiratory	Respiratory function, 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 subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
Primary	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 subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Days -1, 2, 3, 8; Cohort 4: Days -1, 3, 5, 6, 11
Primary	Changes in Physical examination: Body Weight	Body Weight measured in kg, using scale. Assessed as number and percent of subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Days -1, 8; Cohort 4: Days -1, 5, 6
Primary	Pharmacokinetics: AUC	Area Under the Curve (AUC) (0-last): variation of a drug concentration in blood plasma as a function of time, compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
Primary	Pharmacokinetics: Cmax	Cmax - Maximum Concentration of drug substance in blood plasma, compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
Primary	Pharmacokinetics: tmax	tmax - Time to Maximum Concentration of drug substance in blood plasma, compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
Primary	Pharmacokinetics: t1/2	Time to metabolize 1/2 of dose (eg, half-life) of drug substance, measured in blood plasma, compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
Primary	Pharmacokinetics: CL/F	Oral Clearance of the drug substance (CL/F), compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
Primary	Pharmacokinetics: Volume of Distribution (V2/F )	Volume of Distribution of the drug substance (V2/F), compared across treatment and placebo groups.	Cohorts 1, 2, 3: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48 hrs; Cohort 4: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 hrs.
Primary	Pharmacokinetics: Urine presence of MYMD1	urine sample collection for presence of Keystone parent drug - MYMD1 (Isomyosamine)	Cohorts 1, 2, 3, 4: Hours 0-4, 4-8, 8-12, 12-16, 16-24, 24-32, 32-40, 40-48; Additional timepoints for Cohort 4 only: Day 3 - Hours 0-8, 8-16, 16-24, Day 4 - Hours 0-8, 8-16, 16-24, Day 5 - Hours 0-8, 8-16, 16-24.
Primary	Vital signs: Oral Temperature (degrees Centigrade)	Oral temperature, using oral thermometer. Assessed as number and percent of subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
Primary	Vital Signs: Pulse Rate	Pulse rate measured in beats per minute (bpm). Assessed as number and percent of subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
Primary	Vital signs: Blood Pressure	Sitting diastolic and systolic blood pressure, measured by Karotkoff Cuff in mmHg. Assessed as number and percent of subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
Primary	Vital signs: Respiratory Rate	Respiratory rate, measured in breaths per minute (bpm). Assessed as number and percent of subjects with clinically significant changes from Baseline, compared across treatment and Placebo groups.	Cohorts 1, 2, 3: Hours 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 168; Cohort 4: Hours 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 120, 240.
Secondary	Pharmacokinetics: AUC	Area Under the Curve (AUC) (0-last), (0-inf), (0-24): variation of MYMD1 concentration, as a function of time	Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
Secondary	Pharmacokinetics: Cmax	Maximum concentration (Cmax) of MYMD1 in blood plasma	Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
Secondary	Pharmacokinetics: Tmax	Time to maximum concentration (Tmax) of MYMD1 in blood plasma	Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
Secondary	Pharmacokinetics: T1/2	Time to metabolism of half of MYMD1 (eg, half-life) (T1/2) in blood plasma. A minimum of 3 points will be used for estimation	Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
Secondary	Pharmacokinetics: CL/F	Oral clearance (CL/F) of MYMD1	Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
Secondary	Pharmacokinetics: Vz/F	Apparent volume of Distribution of MYMD1	Cohorts 1, 2, 3: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48; Cohort 4: Hours 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96
Secondary	Biomarker Assessment: Tissue Necrosis Factor (TNF) alpha (TNF-a)	Biomarker TNF-a results will be summarized descriptively by dose, using appropriate statistics. Both change from Baseline, expressed as difference (difference between postdose and predose result) as well as the fractional change (postdose/Baseline expressed as percent) will be presented, if appropriate.	Cohorts 1, 2, 3: Hours 2 and 48; Cohort 4: Hours 2, 48, 96, and 120.
Secondary	Biomarker Assessment: Pyridyloxobutyl (POB) adducts in hemophilia	Biomarker Pyridyloxobutyl (POB) adducts in hemophilia results will be summarized descriptively by dose, using appropriate statistics. Both change from Baseline, expressed as difference (difference between postdose and predose result) as well as the fractional change (postdose/Baseline expressed as percent) will be presented, if appropriate.	Cohorts 1, 2, 3: Hours 2 and 48; Cohort 4: Hours 2, 48, 96, and 120.
Secondary	Cardiovascular: QTcF	To quantify the relationship between plasma concentrations of MyMD1 and change from Baseline QTcF. Change from baseline QTcF, derived from locally overread ECGs measured in triplicates.	Cohorts 1, 2, 3: 0.5, 1, 4, 24, 48, 168 hrs; Cohort 4: 0.5, 1, 4, 24, 48, 72, 96, 240 hrs.