Clinical trial NCT04349761: Single Ascending-dose Study to Evaluate Safety, Tolerability, and PK of MYMD1 in Healthy Male Adult Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Undefined
Keywords: Pharmacokinetics
Phase I
First-in-Human
Safety
Tolerability
Hashimoto thyroiditis
Autoimmune
Lead sponsor: TNF Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-16
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled, single ascending dose study.
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events
timeFrame: 5 days
measure: Changes in Physical examination: Neurologic Systems
timeFrame: 5 days
measure: Variation of MyMD1 concentration in blood plasma as a function of time
timeFrame: 5 days
measure: Change from Baseline QTcF and QTcB
timeFrame: 5 days
measure: 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.
timeFrame: 5 days
measure: 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.
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Serum Chemistry: albumin, globulin, Total protein.
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: albumin, globulin, Total protein.
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Serum Chemistry: Electrolytes
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: Electrolytes
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Serum Chemistry: Creatine Kinase muscle/brain (MB) fraction
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Serum Chemistry: Creatine Kinase muscle/brain (MB) fraction
timeFrame: 5 days
measure: 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
timeFrame: 5 days
measure: 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
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Hematology:Red Blood Cell count
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Hematology:Red Blood Cell count
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Hematology: Platelet count, White Blood Cell count
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Hematology: Platelet count, White Blood Cell count
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Hematology: Hematocrit, Reticulocytes
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Hematology: Hematocrit, Reticulocytes
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular volume, Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular volume, Absolute Neutrophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Eosinophils, and Absolute Basophils
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular hemoglobin
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - Hematology: Mean corpuscular hemoglobin
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - coagulation: Fibrinogen
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - coagulation: Fibrinogen
timeFrame: 5 days
measure: Number of Patients with Changes in clinical laboratory values - coagulation: Prothrombin time, Activated partial thromboplastin time, Thrombin time
timeFrame: 5 days
measure: Percentage of Patients with Changes in clinical laboratory values - coagulation: Prothrombin time, Activated partial thromboplastin time, Thrombin time
timeFrame: 5 days
measure: Changes in Physical examination: Cardiovascular
timeFrame: 5 days
measure: Changes in Physical examination: Head, eye, ear, nose, and throat
timeFrame: 5 days
measure: Changes in Electrocardiogram (ECG): Heart Rate
timeFrame: 5 days
measure: Changes in Electrocardiogram (ECG): PR, RR, QRS, QT, QTcF, and QTcB
timeFrame: Time of Assessment (24-Hour Clock)
measure: Vital signs: Oral Temperature (degrees Centigrade)
timeFrame: 5 days
measure: Changes in Physical examination: General Appearance
timeFrame: 5 days
measure: Changes in Physical examination: Respiratory
timeFrame: 5 days
measure: Changes in Physical examination: Gastrointestinal
timeFrame: 5 days
measure: Changes in Physical examination: Body Weight
timeFrame: 5 days
measure: Changes in Physical examination: Height
timeFrame: 5 days
measure: Pharmacokinetics: AUC
timeFrame: 5 days
measure: Pharmacokinetics: Cmax
timeFrame: 5 days
measure: Pharmacokinetics: tmax
timeFrame: 5 days
measure: Pharmacokinetics: t 1/2
timeFrame: 5 days
measure: Pharmacokinetics: CL/F
timeFrame: 5 days
measure: Pharmacokinetics: V2/F
timeFrame: 5 days
measure: Vital Signs: Pulse Rate
timeFrame: 5 days
measure: Vital signs: Blood Pressure
timeFrame: 5 days
measure: Vital signs: Respiratory Rate
timeFrame: 5 days
measure: Thyroid Test: Trilodothyronine (Free T3)
timeFrame: 5 days
measure: Thyroid Test: Thyroxine (Free T4)
timeFrame: 5 days
measure: Thyroid Test: Thyroid Stimulating Hormone (TSH)
timeFrame: 5 days
measure: Urinalysis: Urobilinogen
timeFrame: 5 days
measure: Urinalysis (Microscopic)
timeFrame: 5 days
Secondary outcomes:
Other outcomes:
measure: Biomarker assessment: TNF alpha
timeFrame: 5 days
measure: Biomarker assessment: thyroglobulin
timeFrame: 5 days
measure: Biomarker assessment: TPO antibodies
timeFrame: 5 days
measure: Biomarker assessment
timeFrame: 5 days
Locations:
city: West Palm Beach
country: United States
facility: Palm Beach CRO, LLC
state: Florida
Study officials:
affiliation: Palm Beach CRO, LLC
name: Art Simon, PhD
role: STUDY_DIRECTOR
affiliation: Clinical Research of West Florida
name: Leonard J Dunn, MD
role: PRINCIPAL_INVESTIGATOR
References: